bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent Advances and Challenges of the Drugs Acting on Monoamine Transporters
Authors: Xue Weiwei , Fu Tingting , Zheng Guoxun , Tu Gao , Zhang Yang , Yang Fengyuan , Tao Lin , Yao Lixia , Zhu Feng 
Published: October 2018

Background:
The human Monoamine Transporters (hMATs), primarily including hSERT,
hNET and hDAT, are important targets for the treatment of depression and other behavioral disorders
with more than the availability of 30 approved drugs.

Objective:
This paper is to review the recent progress in the binding mode and inhibitory mechanism of
hMATs inhibitors with the central or allosteric binding sites, for the benefit of future hMATs inhibitor
design and discovery. The Structure-Activity Relationship (SAR) and the selectivity for hit/lead compounds
to hMATs that are evaluated by in vitro and in vivo experiments will be highlighted.

Methods:
PubMed and Web of Science databases were searched for protein-ligand interaction, novel
inhibitors design and synthesis studies related to hMATs.

Results:
Literature data indicate that since the first crystal structure determinations of the homologous
bacterial Leucine Transporter (LeuT) complexed with clomipramine, a sizable database of over 100 experimental
structures or computational models has been accumulated that now defines a substantial degree
of structural variability hMATs-ligands recognition. In the meanwhile, a number of novel hMATs
inhibitors have been discovered by medicinal chemistry with significant help from computational models.

Conclusion:
The reported new compounds act on hMATs as well as the structures of the transporters
complexed with diverse ligands by either experiment or computational modeling have shed light on the
poly-pharmacology, multimodal and allosteric regulation of the drugs to transporters. All of the studies
will greatly promote the Structure-Based Drug Design (SBDD) of structurally novel scaffolds with high
activity and selectivity for hMATs.
Peripheral Immunity, Immunoaging and Neuroinflammation in Parkinson’s Disease
Authors: Kustrimovic Natasa , Marino Franca , Cosentino Marco 
Published: October 2018

:Parkinson’s disease (PD) is the second most common neurodegenerative disorder among elderly population, characterized by the progressive degeneration of dopaminergic neurons in the midbrain. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system (CNS). Nevertheless, numerous evidence has been accumulated in several past years testifying undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. Nevertheless, active participation of immune system as well has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Moreover, infiltration and reactivation of those T cells could exacerbate neuroinflammation to greater neurotoxic levels. Hence, peripheral inflammation is able to prime microglia into pro-inflammatory phenotype, which can trigger stronger response in CNS further perpetuating the on-going neurodegenerative process.:In the present review, the interplay between neuroinflammation and the peripheral immune response in the pathobiology of PD will be discussed. First of all, an overview of regulation of microglial activation and neuroinflammation is summarized and discussed. Afterwards, we try to collectively analyze changes that occurs in peripheral immune system of PD patients, suggesting that these peripheral immune challenges can exacerbate the process of neuroinflammation and hence the symptoms of the disease. In the end, we summarize some of proposed immunotherapies for treatment of PD.
Solid Lipid Nanoparticles and Chitosan-coated Solid Lipid Nanoparticles as Promising Tool for Silybin Delivery: Formulation, Characterization, and In vitro Evaluation
Authors: Piazzini Vieri , Cinci Lorenzo , D'Ambrosio Mario , Luceri Cristina , Bilia Anna Rita , Bergonzi Maria Camilla 
Published: October 2018

Background:
Silybin (Sb) is the major flavolignan of the extract of Silybum marianum.
It is used for the treatment of various acute and chronic liver toxicities, inflammation, fibrosis and
oxidative stress. Many studies indicate that Sb is also active against different carcinomas and it has
been very recently proposed to be beneficial in type 2 diabetes patients. However, Sb is a low water
soluble and low permeable compound.

Objective:
In this study, Solid Lipid Nanoparticles (SLNs) were proposed to enhance the solubility
and the intestinal absorption of Sb.
</P><P>
Methods: SLNs were made of stearic acid and Brij 78 and subsequently coated with chitosan.
Formulations were physically and chemically characterized. Stability studies were also assessed. Sb
in vitro release was evaluated in different pH media. In vitro permeability test with artificial
membranes and Caco-2 cells were performed. Cellular uptake and mucoadhesion studies were
conducted.

Results:
Both nanoparticles were found to be stable. In vitro release indicated that SLNs may prevent
burst release and gastric degradation of Sb. Higher extent of Sb permeation was observed for
both nanoparticles in PAMPA and Caco-2 cell monolayer models. The results of the cellular uptake
study suggested the involvement of active endocytic processes. Chitosan significantly improves
mucoadhesion properties of nanoparticles.
</P><P>
Conclusions: Together with the excellent stability, strong mucoadhesive property, and slow release,
chitosan coated SLNs demonstrated promising potential to enhance absorption of hydrophobic Sb after
oral administration.
Design, Synthesis, and Characterization of Novel Linomide Analogues and their Evaluation for Anticancer Activity
Authors: Priolkar Rudrax N.S. , Shingade Sunil , Palkar Mahesh , Desai Shivalingrao M. 
Published: October 2018

Background:
According to WHO, in 2017, about 90.5 million people suffered from
cancer and about 8.8 million deaths occurred due to disease. Although the chemotherapeutic
agents have decreased the mortality among the cancer patients but high toxicity and non-specific
targets are still major drawbacks.

:
Many researchers have identified linomide, a 4-hydroxy-2-quinolone derivative, as a lead molecule for
the development of anticancer agents. With this background, we thought of the following objective.

Objective:
The objective of this research work involves the synthesis of a series of N-(2-(4-
hydroxy-2-oxo-1-phenyl-1,2-dihydroquinolin-3-yl)-2-oxoethyl)-N-alkyl substituted benzene
sulfonamides IVa-d (1-3) by replacing the anilide moiety at the third position of linomide with
sulfamoylacyl and also N-methyl by N-phenyl functionality. To perform in silico anticancer activity
by using Molegro Virtual Docker (MVD-2013, 6.0) software and in vitro anticancer activity
by MTT assay.

Methods:
The starting material 4-hydroxy-1-phenylquinolin-2(1H)-one was treated with N-bromosuccinamide
to yield compound II. Condensation of compound II with primary amines resulted in
compounds IIIa-d, which, on coupling with substituted aromatic sulfonyl chlorides yield the title
compounds IVa-d (1-3).

Results:
All the synthesized compounds were satisfactorily characterized by spectral data. The results
of docking revealed that the synthesized compounds exhibited well-conserved hydrogen
bonds with one or more amino acid residues in the active pocket of EGFRK tyrosine kinase domain
(PDB ID: 1m17). The MolDock Score of compound IVd-1 (-115.503) was the highest
amongst those tested. The in vitro anticancer activity results showed that compound IVc-1 (R= -
(CH2) 2-CH3 ; R′= -H) and IV d-1 (R= -CH2-C6H5; R′= -H) were found to be most potent against
K562 cell line with an IC50 of 0.451 μM/ml and 0.455 μM/ml respectively. Compound IVd-1 also
showed better potency against A549 cell line with IC50 value of 0.704 μM/ml.

Conclusion:
The results of in silico and in vitro anticancer activity are in agreement with each other.
Compound IV d-1 was found to be most active of the series.
Structure Guided Molecular Docking Assisted Alignment Dependent 3DQSAR Study on Steroidal Aromatase Inhibitors (SAIs) as Anti-breast Cancer Agents
Authors: Banjare Laxmi , Verma Sant Kumar , Jain Akhlesh Kumar , Thareja Suresh 
Published: October 2018

Background:In spite of the availability of various treatment approaches including surgery, radiotherapy, and hormonal therapy, the steroidal aromatase inhibitors (SAIs) play a significant role as chemotherapeutic agents for the treatment of estrogen-dependent breast cancer with the benefit of reduced risk of recurrence. However, due to greater toxicity and side effects associated with currently available anti-breast cancer agents, there is emergent requirement to develop target-specific AIs with safer anti-breast cancer profile.Methods:It is challenging task to design target-specific and less toxic SAIs, though the molecular modeling tools viz. molecular docking simulations and QSAR have been continuing for more than two decades for the fast and efficient designing of novel, selective, potent and safe molecules against various biological targets to fight the number of dreaded diseases/disorders. In order to design novel and selective SAIs, structure guided molecular docking assisted alignment dependent 3D-QSAR studies was performed on a data set comprises of 22 molecules bearing steroidal scaffold with wide range of aromatase inhibitory activity.Results:3D-QSAR model developed using molecular weighted (MW) extent alignment approach showed good statistical quality and predictive ability when compared to model developed using moments of inertia (MI) alignment approach.Conclusion:The explored binding interactions and generated pharmacophoric features (steric and electrostatic) of steroidal molecules could be exploited for further design, direct synthesis and development of new potential safer SAIs, that can be effective to reduce the mortality and morbidity associated with breast cancer.
Intelligent Diabetes Detection System based on Tongue Datasets
Authors: Naveed Safia , Geetha Gurunathan 
Published: October 2018

Background:
Scanning Electron Microscope (SEM) Camera Imaging shows and helps
analyze hidden organs in the human body. SEM image analysis provides in-depth and critical details of organ abnormalities. Similarly, the human tongue finds use in the detection of organ dysfunction with tongue reflexology.

Objective:
To detect diabetes at an early stage using a non-invasive method of diabetes detection
through tongue images and to utilize the reasonable cost of modality (SEM camera) for capturing
the tongue images instead of the existing and expensive imaging modalities like X-ray, Computed
Tomography, Magnetic Resonance Imaging, Positron Emission Tomography, Single-Photon Emission Computed Tomography etc.

Methods:
The tongue image is captured via SEM camera, it is preprocessed to remove noise and
resize the tongue such that it is suitable for segmentation. Greedy Snake Algorithm (GSA) is used
to segment the tongue image. The texture features of the tongue are analyzed and finally it is classified as diabetic or normal.

Results:
Failure of organs stomach, intestine, liver and pancreas results in change of the color of
the tongue, coating thickness and cracks on the tongue. Changes in pancreas proactive behavior also reflect on tongue coating. The tongue coating texture varies from white or vanilla to yellow also
the tongue coating thickness also increases.

Conclusion:
In this paper, the author proposes to diagnose Diabetes Type2 (DT2) at an early stage
from tongue digital image. The tongue image is acquired and processed with Greedy Snake Algorithm (GSA) to extract edge and texture features.
In silico Molecular Modelling of Selected Natural Ligands and their Binding Features with Estrogen Receptor Alpha
Authors: Maruthanila V.L. , Elancheran R. , Roy Nand Kishor , Bhattacharya Anupam , Kunnumakkara Ajaikumar B. , Kabilan S. , Kotoky Jibon 
Published: October 2018

Background:
Breast cancer is one of the most common cancers diagnosed among women. It
is now recognized that two receptors mediate estrogen action and the presence of estrogen receptor alpha
(ER&#945;) correlates with better prognosis and the likelihood of response to hormonal therapy. ER&#945; is
an attractive target for the treatment of breast cancer. Most of the drugs currently used for the breast
cancer treatment have numerous side effects and they are often unsuccessful in removing the tumour
completely. Hence, we focused on natural compounds like flavonoids, polyphenols, etc. which do not
exhibit any high toxic effects against normal cells.
</P><P>
Objectives: To identify the potential natural inhibitors for BCa through an optimised in silico approach.
</P><P>
Methods: Structural modification and molecular docking-based screening approaches were imposed to
identify the novel natural compounds by using Schrödinger (Maestro 9.5). The Qikprop v3.5 was used
for the evaluation of important ADME parameters and its permissible ranges. Cytotoxicity of the
compounds was evaluated by MTT assay against MCF-7 Cell lines.

Results:
From the docking studies, we found that the compounds, Myricetin, Quercetin, Apigenin,
Luteolin and Baicalein showed the highest Glide Scores -10.78, -9.48, -8.92, -8.87 and -8.82 kcal mol-1
respectively. Of these, Luteolin and Baicalein showed the significant IC50 values (25 &#177; 4.0 and 58.3 &#177;
4.4 &#181;M, respectively) against MCF-7 cell line. The ADME profiling of the test compounds was evaluated
to find the drug-likeness and pharmacokinetic parameters.

We mainly focused on in silico study to dock the compounds into the human estrogen receptor
ligand binding domain (hERLBD) and compare their predicted binding affinity with known antiestrogens.
Myricetin, Quercetin, Apigenin, Luteolin and Baicalein were identified as the most promising
among all. Of these, Luteolin and Baicalein showed significant anticancer activities against MCF-7 cell
line. These findings may provide basic information for the development of anti-breast cancer agents.
Low-Cost Synthesis of Gold Nanoparticles from Reused Traditional Gold Leaf and its Application for Sensitive and Selective Colorimetric Sensing of Creatinine in Urine
Authors: Mathaweesansurn Arjnarong , Choengchan Nathawut , Khongkaew Putthiporn , Phechkrajang Chutima M. 
Published: October 2018

Background:
Gold nanoparticles (Au NPs) are normally prepared using standard gold
(III) trichloride which is much expensive and irritant. This work is aimed at demonstrating simple
and low-cost synthesis of Au NPs from the reused traditional gold leaf which is cost-free and less
toxic.

Methods:
The reused gold leaf was donated by the local temple. It was digested and used as the precursor
for the preparation of the Au NPs by Turkevich method. Poly (vinyl alcohol) (PVA) was employed
as a stabilizer. The as-prepared Au NPs were applied for the colorimetric determination of
creatinine in urine without any sample pretreatment.

Results:
Long-term stability of the gold colloids was achieved for at least 3 months. Morphology and
purity of the as-prepared Au NPs were the same as the ones prepared from standard gold (III) salt
and standard gold foil. Colorimetric response of the Au NPs was linear to the standard creatinine up
to 200 mg L-1. The limit of detection (0.16 mg L-1 or 1.41 μM) was enough sensitive for urinary creatinine
detection in patients with kidney disease. Good recoveries (97-108%) and fast analysis time
(3 min) were achieved. The developed method was successfully validated against the HPLC method.

Conclusion:
Facile and cost-effective synthesis of the Au NPs from the reused traditional gold leaf,
was accomplished. The as-prepared Au NPs were successfully applied for the determination of urinary
creatinine with high sensitivity and selectivity.
Computational Approaches Towards Kinases as Attractive Targets for Anticancer Drug Discovery and Development
Authors: Hameed Rabia , Khan Afsar , Khan Sehroon , Perveen Shagufta 
Published: October 2018

Background:
One of the major goals of computational chemists is to determine and develop
the pathways for anticancer drug discovery and development. In recent past, high performance computing
systems elicited the desired results with little or no side effects. The aim of the current review is to evaluate the
role of computational chemistry in ascertaining kinases as attractive targets for anticancer drug discovery and
development.

Methods:
Research related to computational studies in the field of anticancer drug development is reviewed.
Extensive literature on achievements of theorists in this regard has been compiled and presented with special
emphasis on kinases being the attractive anticancer drug targets.

Results:
Different approaches to facilitate anticancer drug discovery include determination of actual targets,
multi-targeted drug discovery, ligand-protein inverse docking, virtual screening of drug like compounds, formation
of di-nuclear analogs of drugs, drug specific nano-carrier design, kinetic and trapping studies in drug design,
multi-target QSAR (Quantitative Structure Activity Relationship) model, targeted co-delivery of anticancer
drug and siRNA, formation of stable inclusion complex, determination of mechanism of drug resistance, and
designing drug like libraries for the prediction of drug-like compounds. Protein kinases have gained enough
popularity as attractive targets for anticancer drugs. These kinases are responsible for uncontrolled and deregulated
differentiation, proliferation, and cell signaling of the malignant cells which result in cancer.

Conclusion:
Interest in developing drugs through computational methods is a growing trend, which saves
equally the cost and time. Kinases are the most popular targets among the other for anticancer drugs which
demand attention. 3D-QSAR modelling, molecular docking, and other computational approaches have not only
identified the target-inhibitor binding interactions for better anticancer drug discovery but are also designing and
predicting new inhibitors, which serve as lead for the synthetic preparation of drugs. In light of computational
studies made so far in this field, the current review highlights the importance of kinases as attractive targets for
anticancer drug discovery and development.
Adipocytokines in Non-functional Adrenal Incidentalomas and Relation with Insulin Resistance Parameters
Authors: Akkus Gamze , Evran Mehtap , Sert Murat , Tetiker Tamer 
Published: October 2018

Objective:
Adrenal incidentalomas are diagnosed incidentally during radiological screenings
and require endocrinological investigations for hormonal activity and malignancy. In certain studies, it
has been reported that non-functional incidentalomas can be associated with high adipocytokines levels
affecting the insulin resistance just like the adipose tissue with metabolic syndrome. Here, we studied
serum adipocytokine levels including leptin, resistin, visfatin, omentin 1 and adiponectin in subjects
with non-functional adrenal incidentaloma.

Methods:
Seventy-seven (77) patients (Female 57; Male 20) with non-functional adrenal incidentaloma
(NFAI) were enrolled in the study. All patients’ past medical history, physical examination including
Body Mass Index (BMI) and waist circumference were performed. The patients’ demographic,
radiologic, hormonal and biochemical parameters were recorded. To compare the parameters, a control
group (CG) (n=30) was formed from healthy volunteers. Both groups were matched for age, gender,
waist circumference and BMI. Serum adipocytokines including leptin, resistin, visfatin, omentin 1 and
adiponectin were measured quantitatively by ELISA. Fasting plasma glucose, insulin, sodium, potassium,
cortisol, adrenocorticotropic hormone (ACTH), lipid profiles, and dehidroepiandrostenedion
sulphate (DHEAS) were measured.

Results:
Mean age of the patients was 52.2±10.4 years. BMI and waist circumference of NFAI patients
were 26.2±3.28 kg/m2 and 90.2 ±7.5cm, respectively. The mean age of the control group was
48.0±8.16. BMI and waist circumference values for the control group were 25.3±3.5 kg/m2 and
88.3±9.6 cm, respectively. When both groups were compared for age, gender, BMI and waist circumference
were non-significant (p>0.05). Serum fasting insulin, total cholesterol, LDL, triglyceride levels
of the NFAI group were significantly higher than CG (p<0.05). The insulin resistance index (HOMAIR)
values of the NFAI subjects were found to be higher than CG (2.5±1.37, 1.1±0.3 p=0.00). Resistin
level of NFAI group was also found to be higher than CG [286.6 ng/L vs. 197 ng/L; (P=0,00)], respectively.
Leptin levels of NFAI were significantly higher than CG [441.1 ng/mL vs. 186.5 ng/mL;
(P=0.00)] respectively. Adiponectin levels were significantly reduced in the NFAI group than in the
CG [10.7 mg/L vs. 30.8 mg/L; (P=0.00)]. Comparision of visfatin and omentin levels was nonsignificant.

Conclusion:
In this study on subjects with non-functional adrenal incidentaloma, we found not only
significantly decreased serum adiponectin levels but also increased leptin, resistin levels as well as
dyslipidemia, hypertension and high insulin resistance index. All of which could affect insulin resistance
and cardiovascular risk factors. The underlying mechanisms of these findings are unknown,
hence further studies are needed.
The Inhibitory Effect of Three Essential Oils on Candida rugosa Lipase: In Vitro and In Silico Studies
Authors: Serseg Talia , Benarous Khedidja , Yousfi Mohamed 
Published: October 2018

Background:Essential oils have been used for centuries. EOs are gaining increasing interest because of their acceptance by consumers and their safe status. For the first time, the effect of essential oils on the inhibition of lipases has been investigated in this work.Objective:We aimed in this study to investigate in vitro the inhibitory effects of the three essential oils of most used spices: Peppermint (Mentha piperita L.), cinnamon (Cinnamomum zeylanicum L.) and Cloves (Syzygium aromaticum L. Merr. et Perry) against Candida rugose lipase. In silico studies using molecular docking have been achieved to study the inhibition mechanism of major compounds of EO: menthol, carvacrol, eugenol and cinnamylaldehyde toward CRL.Methods:The inhibitory effect of three essential oils were determined by candida rugosa enzyme and pNP-L as substrate using spectrophotometry. Autodock vina was used for molecular docking with 50 runs.Results:We have found that these essential oils have a strong inhibitory effect with IC50 values 1.09, 1.78 and 1.13 mg/ml compared with Orlistat 0.06 mg/ml. The results show competitive inhibition for the three major compounds Menthol, Carvacrol and Eugenol with uncompetitive inhibition for Cinnamaldehyde. Different repetition ratios of hydrogen bonds and hydrophobic interactions were observed. The saved interactions were with His449, Ser209, Gly123, Gly124 and Phe344 for all molecules.Conclusion:These observations support using and considering essential oils and their major compounds as good sources for design new drugs to treat candidiasis and other diseases related to Lipases.