bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guest-host Relationship of Cyclodextrin and its Pharmacological Benefits
Authors: Alshati Fatmah , Alahmed Teejan Ameer Abed , Sami Farheen , Ali Md. Sajid , Majeed Shahnaz , Murtuja Sheikh , Hasnain M Saquib , Ansari Mohammed Tahir 
Published: November 2023

Abstract:
Many methods, including solid dispersion, micellization, and inclusion complexes, have been employed
to increase the solubility of potent drugs. Beta-cyclodextrin (βCD) is a cyclic oligosaccharide consisting
of seven glucopyranoside molecules, and is a widely used polymer for formulating soluble inclusion complexes
of hydrophobic drugs. The enzymatic activity of Glycosyltransferase or α-amylase converts starch or
its derivatives into a mixture of cyclodextrins. The βCD units are characterized by α-(1-4) glucopyranose
bonds. Cyclodextrins possess certain properties that make them very distinctive because of their toroidal or
truncated cage-like supramolecular configurations with multiple hydroxyl groups at each end. This allowed
them to encapsulate hydrophobic compounds by forming inclusion complexes without losing their solubility
in water. Chemical modifications and newer derivatives, such as methylated βCD, more soluble hydroxyl propyl
methyl βCD, and sodium salts of sulfobutylether-βCD, known as dexolve® or captisol®, have envisaged
the use of CDs in various pharmaceutical, medical, and cosmetic industries. The successful inclusion of drug
complexes has demonstrated improved solubility, bioavailability, drug resistance reduction, targeting, and
penetration across skin and brain tissues. This review encompasses the current applications of β-CDs in improving
the disease outcomes of antimicrobials and antifungals as well as anticancer and anti-tubercular
drugs.
Prediction of SARS-CoV-2 Infection Phosphorylation Sites and Associations of these Modifications with Lung Cancer Development
Authors: Li Wei , Li Gen , Sun Yuzhi , Zhang Liyuan , Cui Xinran , Jia Yuran , Zhao Tianyi 
Published: November 2023

Introduction:Since the emergence of SARS-CoV-2 viruses, multiple mutant strains have been identified. Infection with SARS-CoV-2 virus leads to alterations in host cell phosphorylation signal, which systematically modulates the immune response.Methods:Identification and analysis of SARS-CoV-2 virus infection phosphorylation sites enable insight into the mechanisms of viral infection and effects on host cells, providing important fundamental data for the study and development of potent drugs for the treatment of immune inflammatory diseases. In this paper, we have analyzed the SARS-CoV-2 virus-infected phosphorylation region and developed a transformer-based deep learning-assisted identification method for the specific identification of phosphorylation sites in SARS-CoV-2 virus-infected host cells.Results:Furthermore, through association analysis with lung cancer, we found that SARS-CoV-2 infection may affect the regulatory role of the immune system, leading to an abnormal increase or decrease in the immune inflammatory response, which may be associated with the development and progression of cancer.Conclusion:We anticipate that this study will provide an important reference for SARS-CoV-2 virus evolution as well as immune-related studies and provide a reliable complementary screening tool for anti-SARS-CoV-2 virus drug and vaccine design.
A Critical Review on Therapeutic Potential of Benzimidazole Derivatives:
A Privileged Scaffold
Authors: Natarajan Ramalakshmi , Kumar Padma , Subramani Arunkumar , Siraperuman Amuthalakshmi , Angamuthu Prabakaran , Bhandare Richie R. , Shaik Afzal B. 
Published: November 2023

Abstract:
Benzimidazole nucleus is a predominant heterocycle displaying a wide spectrum of
pharmacological activities. The privileged nature of the benzimidazole scaffold has been revealed
by its presence in most small molecule drugs and in its ability to bind multiple receptors with high
affinity. A literature review of the scaffold reveals several instances where structural modifications
of the benzimidazole core have resulted in high-affinity lead compounds against a variety of biological
targets. Hence, this structural moiety offers opportunities to discover novel, better, safe and
highly potent biological agents. The goal of the present review is to compile the medicinal properties
of benzimidazole derivatives with a focus on SAR (Structure-Activity Relationships)
Synthesis and Structural Activity Relationship Study of Ursolic Acid
Derivatives as Antitubercular Agent
Authors: Vishwakarma Sadhna , Srivastava Santosh K. , Khare Naveen K. , Chaubey Shiwa , Chaturvedi Vinita , Trivedi Priyanka , Khan Sana , Khan Feroz 
Published: November 2023

Objective:
The chemical transformation of ursolic acid (UA) into novel C-3 aryl ester
derivatives and in vitro and silico assessment of their antitubercular potential.

Background:
UA is a natural pentacyclic triterpenoid with many pharmacological properties. Semisynthetic
UA analogs have demonstrated enhanced anticancer, antimalarial, and antifilarial properties
in our previous studies.

Methods:
The C-30 carboxylic group of previously isolated UA was protected, and various C-3
aryl ester derivatives were semi-synthesized. The agar dilution method was used to evaluate the in
vitro antitubercular efficacy of Mycobacterium tuberculosis (Mtb) H37Ra. In silico docking studies
of the active derivative were carried out against Mtb targets, catalase peroxidase (PDB: 1SJ2), dihydrofolate
reductase (PDB: 4M2X), enoyl-ACP reductase (PDB: 4TRO), and cytochrome bc1
oxidase (PDB: 7E1V).

Results:
The derivative 3-O-(2-amino,3-methyl benzoic acid)-ethyl ursolate (UA-1H) was the most
active among the eight derivatives (MIC1 2.5 μg/mL) against Mtb H37Ra. Also, UA-1H demonstrated
significant binding affinity in the range of 10.8–11.4 kcal/mol against the antiTb target proteins,
which was far better than the positive control Isoniazid, Ethambutol, and co-crystallized ligand
(HEM). Moreover, the predicted hit UA-1H showed no inhibition of Cytochrome P450 2D6
(CYP2D6), suggesting its potential for favorable metabolism in Phase I clinical studies.

Conclusion:
The ursolic acid derivative UA-1H possesses significant in vitro antitubercular potential
with favorable in silico pharmacokinetics. Hence, further in vivo assessments are suggested for
UA-1H for its possible development into a secure and efficient antitubercular drug.
Comprehensive Review on Analytical and Bioanalytical Methods for Quantification of Anti-angiogenic Agents used in Treatment of Cervical
Cancer
Authors: Nisha Parikh , Srushti Parmar , Bhavarth Dave , Kaif Mohammad , Palak Parikh 
Published: November 2023

Abstract:
Cervical cancer is one of the most prevalent forms of cancer occurring across the world
and it has been observed that about 99.7% of cervical cancer cases occur due to infections with the
Human papillomavirus (HPV). Over prolonged durations, cervical cancer can lead to complications
such as vaginal bleeding, itching, and in more severe instances, even the fatality of the individual.
Cervical cancer is an essential cause of death at an early age as it affects young women higher than
other populations. The most frequent drugs used in its treatment include antiangiogenic drugs. This
review summarizes analytical techniques used for the quantification of anti-angiogenic agents-
Bevacizumab, Sunitinib, Pazopanib, Brivanib, and Imatinib. Furthermore, an in-depth description of
numerous techniques including NIR (1), HPLC (10), LC-MS (28), and HPTLC (1) approaches used
to determine and quantify these agents have been provided in this review. Based on the matrix utilized,
the following details were discussed: analytical conditions, detection limits, and solvent used
in sample preparation. Our review holds significant importance within the scientific community,
offering valuable insights into commonly employed measurement techniques and the latest advancements
in these approaches.
A Review of Drug Abuse, Misuse, and Related Laboratory Challenges
Authors: Ranjkeshzadeh Haniye , Sepahi Samaneh , Zare-Zardini Hadi , Taghavizadeh Yazdi Mohammad Ehsan , Ghorani-Azam Adel , Jafari Abbas 
Published: November 2023

Abstract:
Various definitions can be considered for drugs and substance abuse. According to
the National Institute on Abuse, the use of an over-the-counter drug in a different way than that
prescribed to experience or arouse emotion is a simple form of drug abuse. The World Health
Organization (WHO) also defines drug abuse as the persistent or sporadic use of drugs that are
incompatible or unrelated to acceptable medical practice. With the increasing non-therapeutic
use of prescription drugs, serious related consequences have also increased. Therefore, there is a
need to know more precisely about the types of substances and drug abuse, which is the most
important part of diagnosis and recognizing the tests that cause false positive and negative results.
The purpose of this review article is to collect and summarize the most important and more
common types of drugs of abuse and review the drugs that cause false results in screening tests.
In addition, the most common detection methods of the drug will be reviewed and the advantages and drawbacks of each method will be discussed. In this article, we aimed to point out
all the facts about the emerging problems in drug abuse, the methods of screening, and the possible false results in addition to troubleshooting strategies.
Coumarin-derived Hydroxamic Acids as Histone Deacetylase Inhibitors: A Review of
Anti-cancer Activities
Authors: Khai Nguyen Quang , Vu Tran Khac 
Published: November 2023

Abstract:
Since coumarin and hydroxamic acid compounds are well-known in medicinal chemistry, a variety
of their derivatives have been highlighted due to their potential uses for plentiful treatments. Different compounds
of their derivatives acting through diverse activities, such as anti-tumor, anti-cancer, anti-inflammation,
and histone deacetylase inhibition, have been comprehensively investigated by many researchers over the
years. This present review provides the latest literature and knowledge on hydroxamic acids derived from coumarin.
Overall, some recent advancements in biological activities of hybrid derivatives of hydroxamic acids
containing coumarin moieties in medicinal chemistry are discussed.
Role of Enhancing Aerobic Capacity in Countering COVID-19-induced
Liver Injury in Elderlies
Authors: Mohamed Ayman A. , Abdallah Ahmed A. , Jan Yih-Kuen 
Published: November 2023

Abstract::
COVID-19 is still a world disaster; however, its vaccination is globally available.
Liver and gastrointestinal disturbances occur in patients infected with COVID-19 at varying
incidences. Aging decreases the functions of the liver. Thus, the elderly have a weaker response
to the COVID-19 virus. The COVID-19 virus affects the liver directly through direct and indirect
mechanisms. It directly affects the renin-angiotensin system or indirectly causes sepsis, uncontrolled
immune reactions, drug-related hepatic injury, and cytokine storm. Also, COVID-19
vaccines and anti-drugs have adverse effects on the liver too. Thus, this review explores the effect
of enhancing aerobic capacity as a nonpharmacological intervention on decreasing COVID-
19-induced liver injury. Enhancing aerobic capacity decreases COVID-19-induced liver injury
through the following: 1) downregulating systemic and tissue ACE/ANG II/AT1R axis, upregulating
ACE2/ANG 1–7/Mas axis, and moving the renin-angiotensin system to the direction of
the ACE2/ANG (1–7)/Mas axis, 2) Improving mitochondrial function and oxygenation to body
and lung tissues, causing a decrease in harmful oxidative reactions, 3) Increasing the processing
of accumulated free radicals and inhibiting the acute respiratory distress syndrome, 4) Acting as
an antioxidant to protect the liver from oxidative stress, 5) Increasing the effect of antiviral
drugs and COVID-19 vaccines, which improves the function of immune biomarkers, decreases
the viral load, and increases the body's defense against the virus, 6) Decreasing coagulation abnormalities
and thrombosis. In conclusion, enhancing aerobic capacity may be an efficient nonpharmacological
intervention to decrease COVID-19-induced liver injury in elderlies and regenerate
the liver to its normal status after being infected by the COVID-19 virus. It also helps
to strengthen the body's immunity for better effects of both COVID-19 vaccination and drugs.
ADME, Synthesis and Antimycobacterial Activity of 1,2,4-Triazol-3-thiol
Linked Phenylacetamide Derivatives
Authors: Chitre Trupti , Jadhav Shivani , Asgaonkar Kalyani , Pradhan Kunal , Shelke Kalash , Thorat Shubhangi , Bhatambrekar Aniket 
Published: November 2023

Background::
Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is one of the most contagious and fatal human pathogens which necessitates the
development of modified existing drugs or derivatives with action against novel targets.

Aims and Objectives::
In the present work, we have explored a few, 2-(5-(substituted)-4H-1,2,4-triazole-2-ylthio)-N-(substituted) phenyl acetamide (5A-5E) derivatives
as anti-TB.

Materials and Methods::
On the basis of SAR were synthesized and screened against Mycobacterium tuberculosis H37Rv using MABA assay. Their ADME properties were
also checked.

Results::
ADME analysis showed results comparable with standard drug (rifampicin). Derivative 5D turned out to be the most active amongst all the
derivatives with MIC of 0.8μg/ml, comparable to standard drugs like rifampicin(0.8μg/ml) and streptomycin(0.8μg/ml).

Conclusion::
All five compounds have shown excellent inhibitory activity (1.6μg/ml) against the Mycobacterium tuberculosis H37Rv strain. Compound 5D
shows a promising activity (0.8μg/ml) as compared to standard drugs and also it has shown the highest docking score. Literature search has
revealed the presence of 1,2,4-triazole derivatives linked to aromatic link and possessing amide linkage and the presence of Sulphur atom in the
most active derivatives, which supports our designed compounds. Based on these findings, further derivatives would be synthesized and explored
for their role in tuberculosis.
NLRP3 Inflammasome: Key Role in the Pathophysiology of Cardiac Disorders
and its Potential as a Therapeutic Target
Authors: Arora Navneet , Kumar Ranjeet 
Published: November 2023

Abstract:
The NLRP3 inflammasome holds a pivotal position in the pathophysiological landscape of cardiac disorders, presenting itself as a promising
therapeutic target. Central to this role are the proinflammatory cytokines Interleukin (IL)-1 and IL-18, which emerge as major players orchestrated
by the activation of the NLRP3 inflammasome. This activation culminates in pyroptosis, a programmed form of cell death. While controlled
activation of NLRP3 supports tissue repair, its excessive activation yields adverse consequences. Within the spectrum of cardiovascular diseases,
ranging from abdominal aortic aneurysm to calcific aortic valve disease, the NLRP3 inflammasome is notably implicated. Atherosclerosis,
myocardial infarction, diabetic cardiomyopathy, heart failure, and dilated cardiomyopathy collectively contribute to the genesis of inflammatory
conditions. Key to this process is the nucleotide oligomerization domain-containing leucine-rich repeat protein 3 (NLRP3) inflammation,
necessitating both priming and activation signals to orchestrate inflammation. Extensive scientific evidence substantiates the critical role of the
NLRP3 inflammasome in cardiac disorders. Experimental models and clinical studies converge, highlighting its contribution to the intricate web of
inflammatory pathways that underlie cardiac pathologies. This deeper understanding has spurred interest in targeting the NLRP3 inflammasome as
a therapeutic avenue. Efforts to modulate the NLRP3 inflammasome are underway, aiming to temper its hyperactivity without disrupting its
beneficial functions. Strategies involve small molecule inhibitors and biological agents, targeting various points along the signaling cascade. By
selectively intervening in the NLRP3 pathway, researchers aspire to mitigate inflammatory responses, potentially ameliorating the progression of
cardiac disorders. In conclusion, the NLRP3 inflammasome is a central orchestrator in the pathophysiology of diverse cardiac disorders. Its dual
nature, capable of both driving repair and provoking harm, accentuates its significance as a therapeutic target. Scientific endeavors are actively
unraveling its complexities, fostering the development of innovative interventions that could potentially revolutionize the management of cardiac
inflammatory conditions.
Early Prediction of the Chemical Stability of Drug Substances and Drug
Products during the Development Phase
Authors: Tol Trupti , Mhamunkar Swapnil , Tawde Harshad , Samanta Gautam 
Published: November 2023

Background::
Traditional approach to shelf-life prediction claims a substantial amount of product development time, leading to significant delays.

Objective::
The capability of the unconventional Accelerated Stability Assessment Program (ASAP) to decode chemical stability and expedite shelf-life
prediction is discussed in the manuscript.

Methods::
As per the ASAP approach, shelf-life limiting attributes for two APIs’ and a formulation were identified based on the isoconversion ratio.
Isoconversion times at varying accelerated conditions were obtained and the degradation kinetics were modeled using the humidity-modified
Arrhenius equation. R2 and Q2 values were derived to assure model predictability. Temperature and humidity sensitivity of the attributes were
determined from the activation energy; Ea, and humidity sensitivity factor, B, respectively. Degradation plots demonstrated the dynamics of
degradation with time. The predicted values were verified by the available real-time data.

Results::
The degradation rate was modeled for impurities that exhibited conversion substantiated by an isoconversion ratio between 0.25-2.0. The Ea and B
data provided valuable details regarding the sensitivity of the products. Predicted shelf-life of less than a year for the finished product instigated
redevelopment. In the case of the APIs’, the existing storage conditions were found unsuitable for shelf-life stability, and alternate conducive
conditions were identified.

Conclusion::
The study provided cognizance regarding the distinct degradation pattern of an API and its formulation and the contradictory storage requirement
for APIs’ of two different molecules. While the traditional approach claims 3-6 months to predict shelf-life, the ASAP approach provides the same
with enhanced accuracy in just 3-4 weeks.
Development and Characterization of Lipid Nanoparticles Loaded with
Antipsychotic Drugs using Central Composite Design
Authors: Patel Ayushi D. , Modi Chetna D. , Thakkar Vaishali T. , Rana Hardik B. , Chavda Dipika D. 
Published: November 2023

Background:
Fluoxetine and olanzapine combination tablets are available in the
market for oral administration in the treatment of depression, but fluoxetine has been shown to
have a dose-related side effect due to its high oral dose and ability to undergo excessive first-pass
metabolism. Olanzapine has low solubility and low bioavailability.

Objective:
The objective of this study was to prepare lipid nanoparticles containing fluoxetine
and olanzapine to enhance the solubility and dissolution profile of the drugs.

Methods:
Lipid nanoparticles (LNs) were prepared by high-speed homogenization using the ultrasonication method. Different lipids and surfactants were used to screen out the best lipids, surfactants, and their ratio in the preparation of lipid nanoparticles. Drug and polymer compatibil-ity was examined using FTIR and DSC studies. The formulation was optimized using the central composite design to establish functional relationship between independent variables and respons-es. Optimized batch was characterized using particle size, PDI, zeta potential, % EE, % CDR, and stability.

Results:
Phase solubility study revealed FLX to have highest solubility in stearic acid and oleic
acid, whereas OLZ showed highest solubility in Precirol ATO 5 and oleic acid. Poloxamer 188
was selected on the basis of high entrapment efficiency of the drug. In LNs, no significant
interaction between drug and polymer was confirmed by DSC and FTIR. The particle size of
optimized batch was found to be 411.5 nm with 0.532 PDI and - 9.24 mV zeta potential. For FLX
and OLZ, the %EE and %CDR after 8h were found to be more than 90%. No significant change
in %EE and %CDR of the formulation was observed after 4 weeks of storage.

Conclusion:
Experimental results demonstrated excellent drug entrapment as well as controlled
release behavior from optimized LNs of FLX and OLZ at reduced dosage frequency.
Kemampuan Literasi Budaya dan Kewargaan Mahasiswa PGSD Universitas Muhamadiyah Sidoarjo, Indonesia
Authors: Kurniawan Machful Indra 
Published: November 2023

Cultural and civic literacy is part of the national literacy movement launched by the Ministry of Education and Culture in Indonesia. This initiative seeks to equip all Indonesian citizens with the essential skills to navigate and respond to the increasing diversity of the 21st century. The Primary School Teacher Education (PGSD) study program at University Muhammadiyah Sidoarjo (UMSIDA) recognizes the importance of this goal. It provides material content for learning about cultural and civic issues. Based on this, it is essential to conduct research on the cultural literacy and citizenship abilities of PGSD students at Universitas Muhammadiyah Sidoarjo in the 21st century to know the cultural literacy and citizenship abilities of students and provide references to further learning activities in developing cultural literacy and citizenship in PGSD students. The research was conducted in the 2021/2022 academic year, which is between February 2022 and June 2022. This research employed a descriptive study using the survey method with a sample of 136 semester II students who have taken civics courses. Data collection techniques were in the form of questionnaires and data analysis techniques using percentage techniques. The study results showed that the percentage shows 68.4%, namely, out of 136 students, 93 students have a relatively high range of scores in digital literacy skills and citizenship.