bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-Tubercular Activity of Pyrazinamide Conjugates: Synthesis and Structure-Activity Relationship Studies
Authors: Wahan Simranpreet K. , Sharma Sangeeta , Chawla Pooja A.
Published: August 2022

Tuberculosis (TB) is an airborne infection caused by the bacteria Mycobacterium Tuberculosis (MTB). It mainly affects the lungs and causes severe coughing, fever, and chest pains. With the rising prevalence of drug-resistant and inactive Tuberculosis (TB), there is an essential need to discover more effective molecules capable of combating this heinous illness. Pyrazinamide is a first-line tuberculosis therapy that shortens prophylactic duration from twelve to six months. The majority of presently used tuberculosis medications were found by a mix of serendipity and innovative chemical alterations of an existing lead drug. Given that the majority of these discoveries occurred years ago, there is a definite need to use fresh methodologies and technology for discovery to meet the grave danger posed by tuberculosis and the rise of treatment resistance strains. Although current research has provided significant insight into TB transmission, diagnosis, and treatment in the last four years, much more progress is needed to successfully reduce tuberculosis prevalence and eventually eradicate it. The disease continues to be a public health concern, second only to HIV/AIDS in high fatality rates. This review focuses on current efforts to translate the antitubercular activity of all known pyrazinamide analogues and proposes a novel approach for developing new anti-tubercular drugs based on the fusion of pyrazinamide with various heterocyclic rings that shorten treatment for drug-sensitive and multidrug-resistant tuberculosis.
Combinatorial Chemosensitive Nanomedicine Approach for the
Treatment of Breast Cancer
Authors: Gupta Priya , Neupane Yub Raj , Parvez Suhel , Kohli Kanchan , Sultana Yasmin
Published: August 2022

Breast cancer is the most commonly diagnosed type of cancer and ranks
second among cancer that leads to death. From becoming the foremost reason for
global concern, this multifactorial disease is being treated by conventional
chemotherapies that are associated with severe side effects, with chemoresistance
being the ruling reason. Exemestane, an aromatase inhibitor that has been approved by
the US FDA for the treatment of breast cancer in post-menopausal women, acts by
inhibiting the aromatase enzyme, in turn, inhibiting the production of estrogen. However,
the clinical application of exemestane remains limited due to its poor aqueous solubility
and low oral bioavailability. Furthermore, the treatment regimen of exemestane often
leads to thinning of bone mineral density. Thymoquinone, a natural compound derived
from the oil of the seeds of Nigella sativa Linn, possesses the dual property of being a
chemosensitizer and chemotherapeutic agent. In addition, it has been found to exhibit
potent bone protection properties, as evidenced by several studies. To mitigate the
limitations associated with exemestane and to deliver to the cancerous cells overcoming
chemoresistance, the present hypothesis has been put forth, wherein a natural
chemosensitizer and chemotherapeutic agent thymoquinone will be incorporated into a
lipid nanocarrier along with exemestane for combinatorial delivery to cancer cells.
Additionally, thymoquinone being bone protecting will help in ousting the untoward effect
of exemestane at the same time delivering it to the required malignant cells,
safeguarding the healthy cells, reducing the offsite toxicity, and providing potent
synergistic action.
Desonide Nanoemulsion Gel for Transdermal Absorption Drug Delivery:
Pharmacodynamic and Safety Evaluation
Authors: Zhang Jiaqi , Yao Yu , Liu Hanbing , Ma Qiuyan , Huang Lanyi , Chen Yuan , Lin Huaqing
Published: August 2022

Backgrounds:

When administered transdermally, desonide has an unsatisfactory effectiveness due to its poor solubility. As a new transdermal delivery system, nanoemulsion gel has demonstrated significant advantages for drug delivery over conventional formulations. We have established desonide nanoemulsion gel (DES NE gel) for better transdermal absorption, but its efficacy and safety still need to be evaluated. This study aims to provide additional evidence that demonstrating the improved pharmacodynamics and safety of transdermal delivery of Desonide via nanoemulsion gel.

Methods:

Pharmacodynamics and safety of Desonide nanoemulsion gel were evaluated using Desonate® as the reference formulation. To assess the difference in curative effect between DES NE gel and Desonate® and to ensure the safety, the atopic dermatitis (AD) models in KM mice were developed using 2,4-dinitrofluorobenzene (DNFB). The degree of ear swelling, ear mass difference, thymus, spleen index, and HE conventional pathology of mice were used as pharmacodynamic evaluation indexes, and the irritation was predicted by the New Zealand rabbit epidermal stimulation assay.

Results:

Nanoemulsion gels may facilitate transdermal penetration of drugs by influencing the skin condition. Medium and high doses of DES NE gel significantly ameliorated the inflammation and swelling of ear caused by dermatitis/eczema in mice. In addition, compared with DES gel, skin irritation extent did not increase.

Conclusion:

Nanoemulsion gel can be applied to improve the efficacy of drugs with low potency or poor solubility. DES NE gel provides the higher transdermal potential than other delivery systems. In this study, it was found that nano-emulsion gel is a promising percutaneous carrier of DES. DES NE-GEL has significant curative effect on dermatitis/eczema in mouse model, and is expected to provide a new, efficient and low toxic preparation for clinical treatment of dermatitis/eczema through percutaneous system.
An Insight on Novel Approaches & Perspectives for Gastro-Retentive
Drug Delivery Systems
Authors: Dhiman Sonia , Philip Nincy , Gurjeet Singh Thakur , Babbar Ritchu , Garg Nikhil , Diwan Vanshika , Singh Prabha
Published: August 2022

The conventional oral drug delivery systems face a lot of difficulties in the gastrointestinal
tract, such as inappropriate drug release and reduction in the efficacy of the doses, which makes this
system less susceptible to the delivery of drug formulation. For the enhancement of therapeutic efficacy
and bioavailability of the drug, many efforts have been made. The drug candidates which are not stable
at alkaline pH and soluble in acidic medium were selected to increase their therapeutic effectiveness
through gastro retentive drug delivery systems (GRDDS). This article discusses various factors which
alter the gastro retention time (GRT) of the gastro retentive drug delivery system in the stomach and
intestine (duodenum). It emphasizes on the novel approaches made for the delivery and release of drugs
with the use of magnetic systems, floating (low-density) systems, super porous hydrogels, raft systems,
mucoadhesive systems, high-density systems and expandable systems. Along with the applications, the
key aspects of in vivo, in vitro & clinical studies in different approaches to GRDDS have been addressed.
In addition, future perspectives have been summarized to reduce gastric transit time in fasting
and fed conditions.
Research Progress of Plant Active Ingredients in Pharmaceutical Cocrystal
Authors: Wang Zimeng , Shang Hongzhou , Gao Linghuan , Qiao Ning
Published: August 2022

The disadvantages of active ingredients extracted from medicinal plants due to poor solubility in the body and low bioavailability limits their clinical application. Pharmaceutical cocrystal as a new type of drug in solid form has attracted the attention of researchers. This article reviews the effects of cocrystal in various poorly soluble herbal active ingredients of medicinal plants on their physicochemical properties and biological properties, and provides references for the application of pharmaceutical cocrystal in poorly soluble active compounds of medicinal plants.
Pharmacological Activities of the Genus Passiflora (Passifloraceae):
A Patent Review
Authors: Pereira Leal Ana Ediléia Barbosa , de Lavor Érica Martins , de Menezes Barbosa Jackson , de Moura Fontes Araújo Maria Taís , dos Santos Cerqueira Alves Cristiane , de Oliveira Júnior Raimundo Gonçalves , de Lima Ádley Antonini Neves , da Silva Almeida Jackson Roberto Guedes
Published: August 2022

Background:

Passiflora L. is a genus belonging to the Passifloraceae family, with many species widely used in folk medicine and several pharmacological activities described in the scien-tific literature, being a major target for the development of new therapeutic products. Studies have identified several bioactive compounds in their composition as responsible for these activities, mainly C-glycoside flavonoids.

Objective:

The aim of this study was to carry out a review of patents related to the genus and its ap-plication in several pharmacological activities, important for the development of new drugs and formulations.

Method:

The search was carried out in 5 specialized databases, INPI, EPO, WIPO, Latipat and Derwent, using the term ‘Passiflora’ combined with ‘A61K and A61P', subclasses of section A of the International Patent Classification (IPC), which are destined to medical, dental or hygienic pur-poses, and therapeutic activity of chemical compounds or medicinal preparation, respectively.

Results:

1,198 patents citing the genus in the title or abstract have been found, 508 being duplicates. After exclusion and inclusion criteria, 23 patents written in English, Portuguese and Spanish were selected, which demonstrated biological assays in vivo with species of Passiflora as the only active constituent or incorporated in formulations with other compounds.

Conclusion:

The findings of this search showed growing interest in research and industrial areas in the pharmaceutical development with species of Passiflora, suggesting that the different bioactive compounds present in the genus can be considered as an important tool for the development of new effective and safe products with pharmacological potential.
Herbal Medicines for Idiopathic Male Infertility: A Systematic Review
Authors: Bahrami-Taghanaki Hamid Reza , Ahmadian Mohammad , Salari Roshanak , Noras Mohammad Reza
Published: August 2022

Background:

Various medications, surgeries, and assisted reproductive techniques are used to treat male infertility, but the high cost and low effectiveness have made these methods unpopular. the use of herbal medicines such as Withania somnifera, Ceratonia siliqua, Nigella sativa and Alpinia officinarum for the treatment of male infertility has become highly popular in recent years.

Objective:

We conducted this systematic review to evaluate the recent scientific evidence regarding herbal medicines used to treat idiopathic male infertility [IMI].

Method:

Online literature resources were checked using different search engines, including ISI, Web of Knowledge, Medline, PubMed, Scopus, and Google Scholar. Date restrictions were applied to 2020, and the publication language was restricted to English and Persian. The risk of bias was evaluated using the Cochrane method.

Result:

Out of 851 articles, 14 trials with 1218 participants were included. Of the 15 plants and medicinal products introduced in the selected studies, 12 cases were effective in treating male infertility. Each of these plants or products affects specific components of male fertility for which various mechanisms were mentioned, but most of them had antioxidant effects. No serious side effects were reported.

Conclusion:

Whitania somnifera roots, Alpinia officinarum, Nigella sativa seeds, Tomato, and Ceratonia siliqua and the formulation of Xperm, PHF, Churna Ratnam, Svaguptadi Churna, Y virilin capsule, manix capsule, and Tradafertil tablet revealed successful outcomes in treatment of idiopathic male infertility.
Lycopene-Loaded Solid Lipid Nanoparticles: Preparation, Characterization,
ROS-Scavenging, and In vitro Anti-Melanogenesis Evaluations
Authors: Shahraki Omolbanin , Daneshmand Sara
Published: August 2022

Background:

Lycopene, a natural antioxidant from carotenoids, is produced by plants and
microorganisms. It has been investigated in many studies in relation with potential health effects.

Objective:

Due to the high lipid-solubility of lycopene, its skin penetration is challenged. Therefore, in the
present study, lycopene was loaded into lipid nanoparticles to improve penetration and pharmacological
properties.

Methods:

Solid lipid nanoparticles (SLNs) containing lycopene were prepared and anti-tyrosinase properties
were studied in the present study. The formulation was investigated in terms of drug release and antityrosinase
properties. Determination of encapsulation efficiency was performed directly. Electron microscopy
was used to examine the shape of the nanoparticles. Subsequently, the rate of drug release was investigated
by the cell diffusion method. The present study applied cytotoxicity tests, cellular tyrosinase
inhibition, melanin content, and free radical level to evaluate the effect of formulations on melanogenesis
inhibition, and western blot assay was used to determine tyrosinase and MITF levels.

Results:

The results from particle size investigation for LYC-SLNs were 151.1 ± 2.3, and exploring the
data of electron microscopy showed that the shapes of nanoparticles were spherical, and the encapsulation
efficiency was 85.76 ± 2.75%. In determining the anti-tyrosinase effects of LYC-SLNs, a significant reduction
in cellular tyrosinase activity and melanin and ROS levels were observed; It is also worth noting
that LYC-SLNs reduced melanin production with minimal toxicity against melanoma cells.

Conclusion:

In general, the results confirm that SLNs can be an efficient delivery platform for the topical
delivery of lycopene as a natural anti-oxidant and anti-melanogenic agent.
Predicting Binding Affinity Between MHC-I Receptor and Peptides Based on Molecular Docking and Protein-peptide Interaction Interface Characteristics
Authors: Huang Songtao , Ding Yanrui
Published: August 2022

Background:

Predicting protein-peptide binding affinity is one of the leading research subjects in peptide drug design and repositioning. In previous studies, models constructed by researchers just used features of peptide structures. These features had limited information and could not describe the proteinpeptide interaction mode. This made models and predicted results lack interpretability in pharmacy and biology, which led to the protein-peptide interaction mode not being reflected. Therefore, it was of little significance for the design of peptide drugs.

Objective:

Considering the protein-peptide interaction mode, we extracted protein-peptide interaction interface characteristics and built machine learning models to improve the performance and enhance the interpretability of models.

Methods:

Taking MHC-I protein and its binding peptides as the research object, protein-peptide complexes were obtained by molecular docking, and 94 protein-peptide interaction interface characteristics were calculated. Then ten important features were selected using recursive feature elimination to construct SVR, RF, and MLP models to predict protein-peptide binding affinity.

Results:

The MAE of the SVR, RF and MLP models constructed using protein-peptide interaction interface characteristics are 0.2279, 0.2939 and 0.2041, their MSE are 0.1289, 0.1308 and 0.0780, and their R2 reached 0.8711, 0.8692 and 0.9220, respectively.

Conclusion:

The model constructed using protein-peptide interaction interface characteristics showed better prediction results. The key features for predicting protein-peptide binding affinity are the bSASA of negatively charged species, hydrogen bond acceptor, hydrophobic group, planarity, and aromatic ring.
Evaluation of Cytotoxic, COX Inhibitory, and Antimicrobial Activities of
Novel Isoxazole-carboxamide Derivatives
Authors: Hawash Mohammed , Jaradat Nidal , Abualhasan Murad , Qneibi Mohammad , Rifai Hama , Saqfelhait Tala , Shqirat Yaqeen , Nazal Alaa , Omarya Salam , Ibrahim Tymaa , Sobuh Shorooq , Zarour Abdulraziq , Mousa Ahmed
Published: August 2022

Isoxazole derivatives are one of the heterocyclic structures that have various biological activities.

Objective:

This study aimed to design and synthesize novel isoxazole derivatives and evaluate their cytotoxic,
cyclooxygenase (COX) inhibitory, and antimicrobial activities.

Methods:

Coupling reactions of aniline derivatives and isoxazole carboxylic acid have been established to
synthesize chloro-fluorophenyl-isoxazole carboxamide derivatives. The synthesized compounds were
characterized using 1H, 13C-NMR, IR, and HRMS spectrum analysis and evaluated by MTS, COX kit,
and antimicrobial microdilution assays.

Results:

The synthesized compounds showed moderate to potent cytotoxic activity against all the
screened cancer cell lines (except 2b against HepG2) with an IC50 range of 0.107-77.83 μg/ml. The results
showed that the most potent compound against cervical cancer cell line (HeLa) was the 2b compound,
with an IC50 value of 0.11±0.10 μg/ml, which is less than the IC50 for the potent anticancer drug
Doxorubicin. While the 2a and 2b compounds have potential antiproliferative activities against Hep3B
with IC50 doses of 2.774±0.53 and 3.621±1.56 μg/ml, respectively. Furthermore, 2c compound was the
most active against MCF7, with an IC50 value of 1.59±1.60 μg/ml. In addition, the most potent isoxazole
derivative against the COX1 enzyme was the 2b compound, with an IC50 value of 0.391 μg/ml, and compound
2a had a good selectivity ratio of 1.44 compared to the Ketoprofen positive control. However,
compound 2c showed antifungal activity against Candida albicans with an MIC value of 2.0 mg/ml in
comparison to the antifungal drug Fluconazole (MIC = 1.65 mg/ml).

Conclusion:

The synthesized compounds could be candidates for anticancer drugs in the future, and other
analogues and cytotoxicity evaluations should be conducted.
Palladium (Pd)-based Photocatalysts for Suzuki Coupling Reactions: An
Overview
Authors: Boruah Jeena Jyoti , Das Siva Prasad
Published: August 2022

Extensive research has been documented in the last few decades on the utilization of near
IR, visible and UV light in organic chemical transformations. In this brief review, we provide an
overview of the most noteworthy achievements in the area of photocatalytic Suzuki coupling reactions
by palladium (Pd)-based catalytic systems. The works on different types of Pd-based photocatalysts
for Suzuki coupling reaction and their characteristic as well as catalytic activity in terms of substrate
scope, recyclability, TON or TOF are discussed herein.
Multiple Cancer Combating by Natural Bioactives: A Review
Authors: Mishra Rakhi , Singh Ayushi , Mazumder Avijit , Mazumder Rupa , Tiwari Prashant
Published: August 2022

Background:

Significant progress in the field of anticancer research has led to a rise in the study of bioactive chemicals with potential anticancer effects. Still, many bioactive natural chemicals must be investigated in order to generate more effective anti-cancer therapeutics.

Outline:

There have been many attempts to treat cancer, and this review summarizes many bioactive substances obtained from nature that have the ability to fight against different types of malignancies with minimal harm, based on diverse research. Polyphenolic flavonoids, carotenoid (fucoxanthin), tannin, and other notable natural bioactive with anticancer potential were examined and reviewed systematically with an eye toward their significance in many types of cancer treatment.

Conclusion:

Throughout the text, it was concluded that the natural bioactive play a very prominent role in combating different types of cancer, and the information related to the bioactive role in cancer treatment over the last 10 years was gathered from several research and review articles. The material kept in this paper can act as a template for future research in expressing the more beneficial role of other bioactive in acting as an adjuvant in chemotherapy practice for prevention and treatment of various cancer additionally with no or minimal adverse effects which are prominent with the conventional drugs used for the treatment of cancer.
Association between Sleep Duration and Early Pubertal Timing in Children
and Adolescents: A Systematic Review and Meta-analysis
Authors: Hashemipour Mahin , Maracy Mohammad Reza , Mozafarian Nafiseh , Yazdi Maryam , Hovsepian Silva
Published: August 2022

Background:

Early puberty increases the risk of diverse health outcomes during adolescence and beyond. Several studies have explored the links between short sleep duration and early puberty worldwide.

Objective:

The current systematic review and meta-analysis aimed to evaluate the association between sleep duration and early pubertal timing based on published evidence systematically.

Methods:

We searched important electronic databases for articles that reported the association between childhood sleep duration and puberty timing up to October 2020. A total of 848 papers were identified from the databases and manual search. Finally, 10 studies including 23752 participants were included in the meta-analysis. We used the STROBE checklist to assess the quality of the included studies. We calculated the pooled effect sizes using a random or fixed effects model as appropriate.

Results:

Ten studies were eligible for this meta-analysis. There was an inverse significant association between sleep duration and the risk of early puberty, longer duration of sleep was associated with 0.34% decreased odds of early puberty (OR = 0.66, 95% CI = 0.58–0.77, I2 = 96.6%). In a subgroup analysis, when pubertal status was assessed by physical examination compared with Pubertal Development Scale (PDS) or Sexual Maturation Scale (SMS), the associations between sleep duration and age of puberty were attenuated. The pooled OR (95% CI) of studies measuring pubertal timing by PDS/SMS and Tanner stage were 0.50(0.37-0.69) and 0.91(0.77-1.09) respectively. In the subgroup analysis by BMI levels, the pooled OR (95% CI) was slightly attenuated 0.95(0.89-1.01).

Conclusions:

Longer sleep duration is associated with a lower risk of early puberty in children. The association between sleep duration and risk of early puberty may be modified by other factors such as BMI. To clarify the effect of sleep duration on the risk of early puberty in children, further prospective studies are needed.
Association of Asthma with COVID-19 Disease Severity in Pediatric
Patients
Authors: Torabizadeh Mehdi , Heidari Solmaz , Shokouhifar Shokoufeh , Mirkarimi Mohammadreza , Alisamir Mohsen , Mohammadi Shooka
Published: August 2022

Background:

The impact of COVID-19 on asthmatic patients is still uncertain.

Objective:

This study intended to examine the associations between the severity of coronavirus dis-ease 2019 (COVID-19), asthma, and some inflammatory markers among pediatric patients.

Methods:

A retrospective study enrolled pediatric COVID-19 patients who were admitted to Abuzar Hospital (Ahvaz, Iran) during eight months. The diagnosis of COVID-19 was according to the real-time reverse transcription-polymerase chain reaction (RT‐PCR) method. Asthma diagnosis was confirmed by specialists through functional and clinical evaluations (positive bronchodilator reversibility test or positive methacholine challenge test). Demographic and clinical characteristics of the patients were documented. Asthmatic patients with COVID-19 were considered as Group 1 (n= 52) and non-asthmatic COVID-19 patients were assigned as Group 2 (n= 54).

Results:

The mean age of 106 patients was 71.28 ± 50.09 months (range: 1-16 years). Children with severe and moderate COVID-19 had significantly lower levels of neutrophils and lymphocytes, higher inflammatory markers, and longer hospital length of stay (LOS) than patients with a mild course of COVID-19 (p < 0.001). Patients in Group 1 had significantly longer LOS, higher dry cough, chest radiographic findings, fever, levels of D-dimer, fibrinogen, and C-reactive protein (CRP), as well as lower neutrophil and lymphocyte counts, compared with those in Group 2 (p < 0.001).

Conclusion:

The presence of asthma in COVID-19 patients was associated with severe COVID-19 in comparison with their non-asthmatic counterparts. Additional studies with large sample sizes are deemed necessary to determine the impact of asthma on the management and incidence of COVID-19 disease.
CADD Studies in the Discovery of Potential ARI (Aldose Reductase Inhibitors)
Agents for the Treatment of Diabetic Complications
Authors: Gupta Saurabh Kumar , Tripathi Pushpendra Kumar
Published: August 2022

The lack of currently available drugs for treating diabetes complications has stimulated
our interest in finding new Aldose Reductase inhibitors (ARIs) with more beneficial biological
properties. One metabolic method uses aldose reductase inhibitors in the first step of the polyol
pathway to control excess glucose flux in diabetic tissues. Computer-aided drug discovery
(CADD) is key in finding and optimizing potential lead substances. AR inhibitors (ARI) have been
widely discussed in the literature. For example, Epalrestat is currently the only ARI used to treat
patients with diabetic neuropathy in Japan, India, and China. Inhibiting R in patients with severe to
moderate diabetic autonomic neuropathy benefits heart rate variability. AT-001, an AR inhibitor, is
now being tested in COVID-19 to see how safe and effective it reduces inflammation and cardiac
damage. In summary, these results from animal and human studies strongly indicate that AR can
cause cardiovascular complications in diabetes. The current multi-center, large-scale randomized
human study of the newly developed powerful ARI may prove its role in diabetic cardiovascular
disease to establish therapeutic potential. During the recent coronavirus disease (COVID-19) outbreak
in 2019, diabetes and cardiovascular disease were risk factors for severely negative clinical
outcomes in patients with COVID19. New data shows that diabetes and obesity are among the
strongest predictors of COVID-19 hospitalization. Patients and risk factors for severe morbidity
and mortality of COVID- 19.
A Weakly Supervised Brain Tumor Segmentation Strategy Based on Multi-level Sub-category and Membership Matrix
Authors: Li Zi-Wei , Xuan Shi-Bin , Wang Li , Wang Kuan
Published: August 2022

Background:

Using a classification network to generate class activation mapping (CAM) is
a mainstream method for weakly supervised semantic segmentation. However, for brain tumor images,
CAM cannot fit the boundary of the tumor well.

Objective:

To improve the performance of brain tumor CAM, we propose a weakly supervised learning
strategy based on a multi-level sub-category and membership matrix.

Methods:

Firstly, a multi-level sub-category strategy is used to intensively classify the data set. It allows
the convolutional network to learn the in-depth characteristics of the input for enhancing CAM.
Secondly, the idea of fuzzy clustering is introduced into model learning. The membership matrix is
combined with CAM to construct the loss function.

Results:

Exhaustive experiments on the brain tumor dataset BraTS2019 demonstrate that the proposed
method can effectively improve the performance of CAM. Compared with the baseline method, our
approach significantly improved by 17.1% using the common dice similarity coefficient evaluation
approach, and compared with the recent study, our score also improved by almost 9%.

Conclusion:

The proposed methods train the network under image-level labels and help the convolutional
network mine the target boundary information. They can help CAM fit the target border more
accurately.
Design, Synthesis, and Evaluation of Novel Pyruvate Dehydrogenase
Kinase Inhibitors
Authors: Pirotte Bernard , Arslan Deniz , Schoumacher Matthieu , Dilly Sébastien , Elmoualij Benaïssa , Zorzi Danièle , Quatresooz Pascale , Lambert Vincent , Noël Agnès , de Tullio Pascal
Published: August 2022

Aims:

The present work describes the synthesis and the biological evaluation of novel
compounds acting as pyruvate dehydrogenase kinase (PDK) inhibitors. These drugs should become
a new therapeutic approach for the treatment of pathologies improved by the control of the blood
lactate level.

Methods:

Four series of compounds belonging to N-(4-(N-alkyl/aralkylsulfamoyl)phenyl)-2-
methylpropanamides and 1,2,4-benzothiadiazine 1,1-dioxides were prepared and evaluated as PDK
inhibitors.

Results:

The newly synthesized N-(4-(N-alkyl/aralkylsulfamoyl)phenyl)-2-methylpropanamides
structurally related to previously reported reference compounds 4 and 5 were found to be potent
PDK inhibitors (i.e. 10d: IC50 = 41 nM). 1,2,4-Benzothiadiazine 1,1-dioxides carrying a (methyl/
trifluoromethyl)-propanamide moiety at the 6-position were also designed as conformationally
restricted ring-closed analogues of N-(4-(N-alkyl/aralkylsulfamoyl)phenyl)-2-hydroxy-2-methylpropanamides.
Most of them were found to be less potent than their ring-opened analogues. Interestingly,
the best choice of hydrocarbon side chain at the 4-position was the benzyl chain, providing
11c (IC50 = 3.6 μM) belonging to “unsaturated” 1,2,4-benzothiadiazine 1,1-dioxides, and 12c (IC50
= 0.5 μM) belonging to “saturated’ 1,2,4-benzothiadiazine 1,1-dioxides.

Conclusion:

This work showed that ring-closed analogues of N-(4-(N-alkyl/aralkylsulfamoyl) phenyl)-
2-hydroxy-2-methylpropanamides were less active as PDK inhibitors than their corresponding
ring-opened analogues. However, the introduction of a bulkier substituent at the 4-position of the
1,2,4-benzothiadiazine 1,1-dioxide core structure, such as a benzyl or a phenethyl side chain, was
allowed, opening the way to the design of new inhibitors with improved PDK inhibitory activity.
Novel Gatifloxacin3-Carboxamide Derivatives as Anti-Tumor Agents: Synthesis,
Enantioseparation, and Molecular Docking
Authors: Mimouni Fatima. Z. , Belboukhari Nasser , Sekkoum Khaled , Aboul-Enein Hassan Y.
Published: August 2022

Background::

The drug's affinity to the identified target (protein/enzyme) is a critical characteristic in the development of a novel drug. Fluoroquinolone derivatives with a carboxylic group change have improved antimicrobial and anticancer activity while maintaining antibacterial activity similar to parent drugs.

Aim::

The rationale upon which synthesis of the new compounds, evaluation of their anticancer activity with in silico study, and suggestion of their mechanism of action is presented in this paper.

Methods::

This part describes the practical procedures used for the synthesis of four new gatifloxacin 3-carboxamide derivative, with their spectral data (UV-vis, IR, and 1H-NMR).
The enantiosaparation and docking studies are presented and discussed.

Results::

Four gatifloxacin 3-carboxamide derivatives were enantioseparated using a high-performance liquid chromatography approach using two distinct polysaccharide-based chiral stationary phases (CSPs). The baseline enantioseparation of all derivatives evaluated in this study was achieved using both coated and immobilized amylose columns. In silico molecular docking study, revealed that all compounds showed good docking score.

Conclusion::

The novel Fluoroquinolone caboxamides derivatives could be repositioned as DNA topoisomerase II inhibitors, allowing them to be employed as anticancer agents, according to our in silico study.
Experiments in vitro and in vivo are required to confirm their efficacy.
Hot Stage Microscopy-based Method for Determination of Particle Size in
Reverse Engineering: Establishment of a Platform Technology Employing
Carvedilol as a Model Drug
Authors: Deore Jayshri , Rajput Niraj , Jadav Tarang , Sahu Amit Kumar , Sengupta Pinaki
Published: August 2022

Aim:

To develop a hot stage microscopy based method for determination of particle size in reverse engineering and establishment of a platform technology employing carvedilol as a model drug. It was hypothesized that reverse engineering using thermal methods will suggest a logical path in decoding the innovator’s formulation to develop an efficient generic product and preconize the morphology of an active pharmaceutical ingredient (API).

Background:

To develop a generic formulation, a detailed analysis of identification, quantification and characterization of APIs and excipients present in the innovator product is a mandatory requirement. Identification of actives, excipients, and manufacturing processes involved in innovator product formulation can be facilitated using reverse engineering studies.

Objective:

The objective of this study was to establish a platform technology for determination of particle size in reverse engineering using hot stage microscopy (HSM).

Method:

Method: Differential scanning calorimetry (DSC) and HSM techniques were employed for identification of different unit processes that can affect the particle size distribution of API during formulation.

Result:

Result: DSC technique helped to unwind information about qualitative as well as quantitative nature of the formulation blend. HSM technique helped to reveal the particulate level properties of the drug present in the blend and formulation.

Conclusion:

The study concluded that the two thermal techniques DSC and HSM together could be effectively used to reverse engineer a given formulation using a very less sample quantity. The study suggested a logical path in decoding innovator’s formulation to develop an efficient generic product. Moreover, this HSM based thermal method of particle size determination will offer new insight into the decoding of an innovator product in a shorter period.
Nanomaterial-based Electrochemical Biosensors
Authors: Şensoy Kübra Gençdağ , Akpınar Fatma , Muti Mihrican
Published: August 2022

Nanomaterials often show very different sizes, shapes, and stability properties. They also
facilitate electron transfer and can be easily modified with chemical ligands and biomolecules. These
properties, combined with the ease of miniaturizing nanoscales and their application to sensing
devices, make nanomaterials well suited for essential chemical/biochemical sensing applications.

:

Nanomaterials are superior materials not only due to their structural properties but also their functional
properties. Using various methods makes it possible to change the available and stack properties.

:

Nano-sized materials are preferred in modern technological systems because they have a large surface
area and different optical and electronic properties.

:

In this study, electrochemical biosensor applications based on sensors modified with various nanomaterials
were evaluated in terms of analytical parameters, such as detection limit, linear range, and
features, such as easy fabrication, storage stability, and reproducibility. Besides, the advantages of
using nanomaterials were examined under 6 different headings as enzyme biosensors, immunosensors,
nucleic acid sensors, cell, phage, and aptasensors.
Recent Advances of Nanotechnology in Brain Targeting
Authors: Dewangan Hitesh Kumar , Singh Vanshita , Garg Akash , Sharma Rajeev
Published: August 2022

Central nervous system disorders, particularly neurodegenerative disorders, are a serious public health concern that researchers must address to protect the persons against them. The
prevalence of the blood-brain barrier (BBB), which segregates the blood from cerebral parenchyma and hence limits the brain uptake of most of the therapeutic agents, makes developing drug
delivery systems for brain delivery one of the most challenging research subjects in pharmaceutical domains. The detailed description of BBB-crossing nanotechnology in this article is expected
to pique the attention of researchers from a wide range of fields who want to help build powerful
BBB-crossing nanosystems for highly effective brain targeting. Recent advances in nanotechnology have resulted in multifunctional nanosystems that can cross or circumvent the BBB, allowing
for more accurate assessment and treatment of brain tumours. The application of nanotechnology
in targeting different drugs across the brain is included in this review.
Computational Modelling Strategies for Exploring Triazolopyridazine PIM1 Kinase Inhibitors as Anticancer Agents
Authors: Walhekar Vinayak , Bagul Chandrakant , Kumar Dileep , Achaiah Garlapati , Muthal Amol , Kulkarni Ravindra , Basavarju Maccha
Published: August 2022

Background:

PIM (Proviral Integration site for Moloney Murine Leukemia virus) kinases are members of
the class of kinase family serine/threonine kinases, which play a crucial role in cancer development. As there is no drug
in the market against PIM-1, kinase has transpired as a budding and captivating target for discovering new anticancer
agents targeting PIM-1 kinase.

Aim:

The current research pondered the development of new PIM-1 kinase inhibitors by applying a ligand-based and
structure-based drug discovery approach involving 3D QSAR, molecular docking, and dynamics simulation.

Methods:

In this study, association allying the structural properties and biological activity was undertaken using 3DQSAR
analysis. The 3D-QSAR model was generated with the help of 35 compounds from which the best model manifested
an appreciated cross-validation coefficient (q2) of 0.8866 and conventional correlation coefficient (r2) of 0.9298,
respectively and the predicted correlation coefficient (r2
pred) was obtained as 0.7878.

Results:

The molecular docking analysis demonstrated that the analogs under analysis occupied the active site of the
PIM-1 kinase receptor and interactions with Lys67 in the catalytic region, Asp186 in the DFG motif, and Glu171 were
noticed with numerous compounds.

Discussion:

Furthermore, the molecular dynamics simulation study stated that the ligand portrayed strong conformational
stability within the active site of PIM-1 kinase protein, forming two hydrogen bonds until 100 ns, respectively.

Conclusion:

Overall outcomes of the study revealed that applications of the ligand-based drug discovery approach and
structure-based drug discovery strategy conceivably applied to discovering new PIM-1 kinase inhibitors as anticancer
agents.
The mRNA Expression of PTEN, LEF1, JAK3, LC3 and p62/SQSTM1
Genes in Patients with Chronic Myeloid Leukemia
Authors: Sharifzadeh Sedigheh , Lak Elahe Razmara , Tamaddon Gholamhossein , Ramzi Mani , Ranjbaran Reza , Abedi Elham
Published: August 2022

Introduction:

Chronic myeloid leukemia (CML) is a progressive myeloproliferative
disorder resulting from forming a chimeric BCR-ABL gene. The proteins derived from this gene
can affect some genes from various signaling pathways such as PI3K/AKT/Wnt/catenin/JAK/Stat
involved in proliferation, differentiation, cell death, and genes related to autophagy. Imatinib is the
first-line treatment for CML patients, with durable and proper responses in Iranian children and
adult CML patients. Hence, we aimed to evaluate the mRNA expression of some selected key
genes from those pathways in patients with CML before and under treatment.

Methods:

In the case-control study, the mRNA expression of PTEN, LEF1, JAK3, LC3 and p62
genes were measured in 51 CML patients (6 patients before treatment and 45 patients under treatment
with imatinib mesylate) and 40 healthy controls using the Real-time PCR method.

Results:

The mRNA expression of PTEN and P62 were significantly higher in newly diagnosed
patients than in controls (P<0.0001 and P = 0.0183, respectively), while the expression of the LC3
gene was significantly lower in the untreated newly diagnosed group than in control subjects (P =
0.0191). The expression level of PTEN, LEF1, JAK3 and P62 genes were significantly decreased
in patients under treatment than in the group before treatment (P = 0.0172, P = 0.0002, P = 0.0047
and P = 0.0038, respectively). A positive correlation was seen between the gene expression of P62
and BCR-ABL in the patients under treatment (r 0529, P = 0.016).

Conclusion:

Our findings showed that the changes in expression of these genes were related to the
patient’s treatment. Due to the key role of these genes in proliferation, differentiation and tumor
suppression, it is proposed that these genes may be helpful for follow-up of treatment in CML
patients.
A Comprehensive Review on COVID-19: Emphasis on Current Vaccination
and Nanotechnology Aspects
Authors: Dewangan Hitesh Kumar , Rai Akriti , Shah Kamal , Sharma Rajiv
Published: August 2022

COVID-19, caused by the SARS-CoV-2 virus, has been expanding. SARS-CoV caused
an outbreak in early 2000, while MERS-CoV had a similar expansion of illness in early 2010. Nanotechnology
has been employed for nasal delivery of drugs to conquer a variety of challenges that
emerge during mucosal administration. The role of nanotechnology is highly relevant to counter this
“virus” nano enemy. This technique directs the safe and effective distribution of accessible therapeutic
choices using tailored nanocarriers, as well as the interruption of virion assembly, by preventing
the early contact of viral spike glycoprotein with host cell surface receptors. This study summarises
what we know about earlier SARS-CoV and MERS-CoV illnesses, with the goal of better understanding
the recently discovered SARS-CoV-2 virus. It also explains the progress made so far in
creating COVID-19 vaccines/ treatments using existing methods. Furthermore, we studied nanotechnology-
based vaccinations and therapeutic medications that are now undergoing clinical trials
and other alternatives.
A Sequential Pattern-Based Method for Mining Technological Context and
Developing R&D Strategies for the Cloud Computing Industry
Authors: Huang Jia-Yen , Zhuang Pei-Hua
Published: August 2022

Aim:

Cloud computing has been a hot topic in recent years, yet its technology trend is
rarely comprehensively studied in peer-reviewed publications. Owing to a great number of professional and technical terms and the increasing volume of technical data presented in patents, it is difficult to analytically identify the timeframe of technological development.

Methods:

To remedy this problem, this study uses a sequential pattern method and social network
analysis to develop the technological context of cloud computing.

Results & Discussion:

The analysis of relative patent position, technology quality, and technology
life cycle was incorporated.

Conclusion:

This study proposes a method of patent portfolio analysis on the technological level to
assist managers of cloud computing enterprises in developing competitive research and development
(R&D) strategies.
Single Cell Protein for Foods and Feeds: A Review of Trends
Authors: Onyeaka Helen , Anumudu Christian K. , Okpe Calistus , Okafor Arthur , Ihenetu Francis , Miri Taghi , Odeyemi Olumide A. , Anyogu Amarachukwu
Published: August 2022

Introduction:

Predictions on the world’s population in the next few decades suggest that the global demand for animal-derived proteins may not be met if current conventional agriculture approaches are used. One promising solution to this complex crisis lies in the use of single-cell proteins (SCP). SCP refers to the edible biomass of unicellular microorganisms and can be developed as animal feeds or human foods. This paper provides a detailed overview on research towards the production and utilisation of SCPs and trends within the field.

Study Design:

A bibliometric based study was conducted on 425 SCP research articles collected from the Web of Science database, analysing the most cited papers using VOSviewer software, and contributing authors, affiliations and country of origin. Research publications on SCP started in 1961 and has grown steadily over the years.

Discussion:

Emerging research topics within SCP production focused on the use of improved fungal strains, the composition and characteristics of SCPs based on the type of substrates used, industrial production processes and the use of waste for SCP production, which serves the dual purpose of mitigating the cost associated with waste disposal and production of a valuable product.
Modulation of Lignin and its Implications in Salt, Drought and Temperature
Stress Tolerance
Authors: Kavi Kishor P.B.  , Srinivas B.  , Singam Prashant , Sahitya G.  , Tulya Rupa Sri V.  , G. Rajasheker , Suravajhala Prashanth
Published: August 2022

Background:

Lignins are phenylpropanoid polymers with complex composition and structures
and crucial components in plant cell walls. Lignins are biosynthesized from oxidative polymerization
of 4-hydroxycinnamyl alcohols, but differ in the degree of methoxylation.

Objective:

This review makes an endeavour to identify the gaps in our understanding of lignin modulation
and gain insights into their relevance to abiotic stress tolerance.

Methods:

Critical review of the recent literature to understand the regulation of lignin, the major biopolymer
involved in a multitude of functions.

Results:

Lignin contributes to the growth of tissues, and organs that give mechanical protection or
lodging resistance and also responds to multiple biotic and abiotic stresses. The quantity and quality of
accumulation of lignin is dependent on the type of plant species and abiotic stress. In this review, we
briefly discuss the biosynthesis, modulation of lignin by diverse transcription factors and its role in
salt, drought and temperature stress tolerance.

Conclusion:

We need to explore many areas to gain comprehensive knowledge about the secondary
cell wall deposition of monolignols, and their transport, leading to lignin accumulation which imparts
biotic and abiotic stress tolerance to plants.
Synthesis, Characterization, Textile Dyeing Study and Antimicrobial
Activity of 3-(1H-benzo[d]imidazol-2-yl)-2-chloroquinoline
Authors: Maru Minaxi S. , Kaur Varinder , Behal Jagriti , Vaid Samriti
Published: August 2022

Background:

Benzimidazoles are important heterocyclic compounds having significant
attention in the pharmacological industry due to their various biological and dying properties.

Objective:

3-(1H-benzo[d]imidazol-2-yl)-2-chloroquinoline, a heterocyclic dye (1), was prepared
using o-phenylenediamine and 2-chloroquinoline-3-carbaldehyde in the presence of ceric
ammonium nitrate catalyst and hydrogen peroxide under reflux condition, which was subjected to
mordant and disperse dyeing study and antimicrobial activity to develop antimicrobial textile
garment products.

Methods:

Elemental analysis, NMR, FT-IR, Mass and UV-visible spectroscopic techniques were
used to characterize dye (1). Polyester, wool and silk textile fabrics were selected for the
evaluation of dyeing assessment of dispersed heterocyclic dye. The in vitro antimicrobial screening
was done against Mycobacterium tuberculosis H37Rv, Streptococcus pyogenes, Staphylococcus
aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, Aspergillus niger and
Aspergillus clavatus strains using standard drugs as reference.

Results:

The deep brown to green shades were observed for dye (1), particularly on polyester
samples and showed excellent wash fastness and light fastness properties. Dye (1) was active
against Staphylococcus aureus showing 100 µgmL-1 MIC with 16.5 mm ZOI better than the
reference drug ampicillin. It was more active against Candida albicans with 12.5, µgmL-1 MIC
with 33 mm ZOI in compared to nystatin reference drug during antifungal screening. In primary
screening, the MIC value for antimycobacterial activity was <12.5 µgmL-1
.

Conclusion:

The characteristics values of spectroscopic data support the chemical structure of dye
(1). It may become the potent applicant for the production of antimicrobial textile garment products
like socks, stockings, caps, etc. due to its fastness, lightning and antimicrobial activity results.