“Analysis of binding properties of integrase protein to find out potential drug candidate for HIV-2 through insilico molecular docking ”

Introduction: Mycobacterium tuberculosis has instigated a serious challenge toward the effective treatment of tuberculosis. The reoccurrence of the resistant strains of the disease to accessible drugs/medications has mandate for the development of more effective anti-tubercular agents with efficient activities. Time expended and costs in discovering and synthesizing new hypothetical drugs with improved biological activity have been a major challenge toward the treatment of multi-drug resistance strain M. tuberculosis (TB). Meanwhile, to solve the problem stated, a new approach i.e. QSAR which establish connection between novel drugs with a better biological against M. tuberculosis is adopted. Methods: The anti-tubercular model established in this study to forecast the biological activities of some anti-tubercular compounds selected and to design new hypothetical drugs is subjective to the molecular descriptors; MATS7s, SM1_DzZ, SpMin4_Bhv, TDB3v and RDF70v. Ligand-receptor interactions between quinoline derivatives and the receptor (DNA gyrase) was carried out using molecular docking technique by employing the PyRx virtual screening software and discovery studio visualizer software. Furthermore, docking study indicates that compounds 20 of the derivatives with promising biological activity have the utmost binding energy of -17.79 kcal/mol. Results: Meanwhile, the interaction of the standard drug; isoniazid with the target enzyme was observed with the binding energy -14.6 kcal/mol which was significantly lesser than the binding energy of the ligand (compound 20).Therefore, compound 20 served as a template structure to designed compounds with more efficient activities. Among the compounds designed; compounds 20p was observed with better anti-tubercular activities with more prominent binding affinities of -24.3kcal/mol. Conclusion: The presumption of this research aid the medicinal chemists and pharmacist to design and synthesis a novel drug candidate against the tuberculosis. Moreover, in-vitro and in-vivo test could be carried out to validate the computational results.

Download Full-text

Synthesis and Anticancer Activity of 9-O-Pyrazole Alkyl Substituted Berberine Derivatives

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180717121208 ◽

2019 ◽

Vol 18 (11) ◽

pp. 1639-1648 ◽

Cited By ~ 5

Author(s):

Daipeng Xiao ◽

Fen He ◽

Dongming Peng ◽

Min Zou ◽

Junying Peng ◽

...

Keyword(s):

Oxidative Stress ◽

Molecular Docking ◽

Anticancer Activity ◽

Cell Lines ◽

Human Lung Cancer ◽

Drug Candidate ◽

Molecular Docking Study ◽

Protective Function ◽

Anti Cancer ◽

Cancer Activity

Background: Berberine (BBR), an isoquinoline plant alkaloid isolated from plants such as Coptis chinensis and Hydrastis canadensis, own multiple pharmacological activities. Objective: In this study, seven BBR derivatives were synthesized and their anticancer activity against HeLa cervical and A549 human lung cancer cell lines were evaluated in vitro. Methods: The anti-cancer activity was measured by MTT assay, and apoptosis was demonstrated by the annexin V-FITC/PI staining assay. The intracellular oxidative stress was investigated through DCFH-DA assay. The molecular docking study was carried out in molecular operating environment (MOE). Results: Compound B3 and B5 showed enhanced anti-cancer activity compared with BBR, the IC50 for compound B3 and B5 were significantly lower than BBR, and compound B3 at the concentration of 64 or 128 µM induced apoptosis in HeLa and A549 cell lines. The reactive oxygen species (ROS) was generated in both cell lines when treated with 100 µM of all the compounds, and compound B3 and B5 induced higher activity in the generation of ROS, while compound B3 exhibited the highest activity, these results are in accordance with the cytotoxicity results, indicating the cytotoxicity were mostly generated from the oxidative stress. In addition, molecular docking analysis showed that compound B3 had the greatest affinity with Hsp90. Upon binding, the protective function of Hsp90 was lost, which might explain its higher cytotoxicity from molecular interaction aspect. Conclusion: All the results demonstrated that compound B3 and B5 showed significantly higher anti-cancer ability than BBR, and compound B3 is a promising anticancer drug candidate.

Download Full-text

[Cu(dipicolinoylamide)(NO3)(H2O)] as anti-COVID-19 and antibacterial drug candidate: Design, Synthesis, Crystal Structure, DFT and Molecular Docking

Journal of Molecular Structure ◽

10.1016/j.molstruc.2021.131348 ◽

2021 ◽

pp. 131348

Author(s):

Laila H. Abdel-Rahman ◽

Maram T. Basha ◽

Badriah Saad Al-Farhan ◽

Mohamed R. Shehata ◽

Shaaban K. Mohamed ◽

...

Keyword(s):

Crystal Structure ◽

Molecular Docking ◽

Drug Candidate ◽

Antibacterial Drug ◽

Design Synthesis

Download Full-text

The Leukotriene Receptor Antagonist Montelukast Attenuates Neuroinflammation and Affects Cognition in Transgenic 5xFAD Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22052782 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2782 ◽

Cited By ~ 1

Author(s):

Johanna Michael ◽

Julia Zirknitzer ◽

Michael Stefan Unger ◽

Rodolphe Poupardin ◽

Tanja Rieß ◽

...

Keyword(s):

T Cells ◽

Receptor Antagonist ◽

Cd8 T Cells ◽

Disease Model ◽

Cognitive Outcome ◽

Drug Candidate ◽

Potential Drug ◽

Leukotriene Receptor Antagonist ◽

Leukotriene Receptor ◽

5Xfad Mice

Alzheimer’s disease (AD) is the most common form of dementia. In particular, neuroinflammation, mediated by microglia cells but also through CD8+ T-cells, actively contributes to disease pathology. Leukotrienes are involved in neuroinflammation and in the pathological hallmarks of AD. In consequence, leukotriene signaling—more specifically, the leukotriene receptors—has been recognized as a potential drug target to ameliorate AD pathology. Here, we analyzed the effects of the leukotriene receptor antagonist montelukast (MTK) on hippocampal gene expression in 5xFAD mice, a commonly used transgenic AD mouse model. We identified glial activation and neuroinflammation as the main pathways modulated by MTK. The treatment increased the number of Tmem119+ microglia and downregulated genes related to AD-associated microglia and to lipid droplet-accumulating microglia, suggesting that the MTK treatment targets and modulates microglia phenotypes in the disease model compared to the vehicle. MTK treatment further reduced infiltration of CD8+T-cells into the brain parenchyma. Finally, MTK treatment resulted in improved cognitive functions. In summary, we provide a proof of concept for MTK to be a potential drug candidate for AD and provide novel modes of action via modulation of microglia and CD8+ T-cells. Of note, 5xFAD females showed a more severe pathology, and in consequence, MTK treatment had a more pronounced effect in the females compared to the males. The effects on neuroinflammation, i.e., microglia and CD8+ T-cells, as well as the effects on cognitive outcome, were dose-dependent, therefore arguing for the use of higher doses of MTK in AD clinical trials compared to the approved asthma dose.

Download Full-text

Structure based pharmacophore modeling, virtual screening, molecular docking and ADMET approaches for identification of natural anti-cancer agents targeting XIAP protein

Scientific Reports ◽

10.1038/s41598-021-83626-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Firoz A. Dain Md Opo ◽

Mohammed M. Rahman ◽

Foysal Ahammad ◽

Istiak Ahmed ◽

Mohiuddin Ahmed Bhuiyan ◽

...

Keyword(s):

Molecular Docking ◽

Virtual Screening ◽

Md Simulation ◽

Pharmacophore Model ◽

Pharmacophore Modeling ◽

Drug Candidate ◽

Inhibitor Of Apoptosis ◽

Inhibitor Of Apoptosis Protein ◽

Apoptosis Protein ◽

Apoptosis Process

AbstractX-linked inhibitor of apoptosis protein (XIAP) is a member of inhibitor of apoptosis protein (IAP) family responsible for neutralizing the caspases-3, caspases-7, and caspases-9. Overexpression of the protein decreased the apoptosis process in the cell and resulting development of cancer. Different types of XIAP antagonists are generally used to repair the defective apoptosis process that can eliminate carcinoma from living bodies. The chemically synthesis compounds discovered till now as XIAP inhibitors exhibiting side effects, which is making difficulties during the treatment of chemotherapy. So, the study has design to identifying new natural compounds that are able to induce apoptosis by freeing up caspases and will be low toxic. To identify natural compound, a structure-based pharmacophore model to the protein active site cavity was generated following by virtual screening, molecular docking and molecular dynamics (MD) simulation. Initially, seven hit compounds were retrieved and based on molecular docking approach four compounds has chosen for further evaluation. To confirm stability of the selected drug candidate to the target protein the MD simulation approach were employed, which confirmed stability of the three compounds. Based on the finding, three newly obtained compounds namely Caucasicoside A (ZINC77257307), Polygalaxanthone III (ZINC247950187), and MCULE-9896837409 (ZINC107434573) may serve as lead compounds to fight against the treatment of XIAP related cancer, although further evaluation through wet lab is necessary to measure the efficacy of the compounds.

Download Full-text

Hypoglycemic, hepatoprotective and molecular docking studies of 5-[(4-chlorophenoxy) methyl]-1, 3, 4-oxadiazole-2-thiol

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v13i2.35514 ◽

2018 ◽

Vol 13 (2) ◽

pp. 149 ◽

Cited By ~ 1

Author(s):

Naureen Shehzadi ◽

Khalid Hussain ◽

Nadeem Irfan Bukhari ◽

Muhammad Islam ◽

Muhammad Tanveer Khan ◽

...

Keyword(s):

Molecular Docking ◽

Video Clip ◽

Serum Levels ◽

Docking Studies ◽

Normal Serum ◽

Yeast Cells ◽

Drug Candidate ◽

Molecular Docking Studies

The present study aimed at the evaluation of anti-hyperglycemic and hepatoprotective potential of a new drug candidate, 5-[(4-chlorophenoxy) methyl]-1,3,4-oxadiazole-2-thiol (OXCPM) through in vitro and in vivo assays, respectively. The compound displayed excellent dose-dependent ɑ-amylase (28.0-92.0%), ɑ-glucosidase (40.3-93.1%) and hemoglobin glycosylation (9.0%-54.9%) inhibitory effects and promoted the uptake of glucose by the yeast cells (0.2 to 26.3%). The treatment of the isoniazid- and rifampicin- (p.o., 50 mg/kg of each) intoxicated rats with OXCPM (100 mg/kg, p.o.) resulted in restoring the normal serum levels of the non-enzymatic (total bilirubin, total protein and albumin) and bringing about a remarkable decrease in the levels of enzymatic (alanine transaminases, aspartate transaminases and alkaline phosphatase) biomarkers. The molecular docking studies indicated high binding affinity of the compound for hyperglycemia-related protein targets; fructose-1,6-bisphosphatase, beta2-adrenergic receptors and glucokinase. The results indicate that OXCPM may not only reduce hyperglycemia by enzyme inhibition but also the disease complications through protection of hemoglobin glycosylation and hepatic injury.Video Clip of Methodology:Glucose uptake by yeast cells: 4 min 51 sec <a href="https://www.youtube.com/v/8cJkuMtV0Wc">Full Screen</a> <a href="https://www.youtube.com/watch?v=8cJkuMtV0Wc">Alternate</a>

Download Full-text

In Silico Drug Designing of Protease Inhibitors to Find the Potential Drug Candidate for HIV1

Computational Biology and Bioinformatics ◽

10.11648/j.cbb.20130103.11 ◽

2013 ◽

Vol 1 (3) ◽

pp. 10 ◽

Cited By ~ 1

Author(s):

Alka Dwivedi

Keyword(s):

Protease Inhibitors ◽

In Silico ◽

Drug Candidate ◽

Potential Drug ◽

Drug Designing

Download Full-text

Synthesis, Crystal Structure, Inhibitory Activity and Molecular Docking of Coumarins/Sulfonamides Containing Triazolyl Pyridine Moiety as Potent Selective Carbonic Anhydrase IX and XII Inhibitors

Crystals ◽

10.3390/cryst11091076 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1076

Author(s):

Yassine Aimene ◽

Romain Eychenne ◽

Frédéric Rodriguez ◽

Sonia Mallet-Ladeira ◽

Nathalie Saffon-Merceron ◽

...

Keyword(s):

Molecular Docking ◽

Carbonic Anhydrase ◽

Inhibitory Activity ◽

Cancer Drug ◽

Drug Candidate ◽

Coumarin Derivatives ◽

X Ray Diffraction ◽

Rhenium Complex ◽

Pyridine Moiety ◽

Docking Calculations

In this work, two classes of Carbonic Anhydrase (CA) inhibitors, sulfonamide and coumarin derivatives linked to pyta moiety (2a-b) and their corresponding rhenium complexes (3a-b), were designed. These compounds were synthesized and fully characterized by classical analytical methods and X-ray diffraction. All the synthesized compounds were evaluated for their inhibitory activity against the hCA isoforms I, II, IX and XII. They exhibited high inhibitory activities in the range of nanomolar for both hCA IX and hCA XII isoforms. The sulfonamide compound 2a showed the strongest inhibition against the tumour-associated hCA IX isoform with a Ki of 11.7 nM. The tumour-associated isoforms hCA IX and hCA XII were selectively inhibited by all the coumarin derivatives, with inhibition constants ranging from 12.7 nM (2b) to 44.5 nM (3b), while the hCA I and II isoforms were slightly inhibited (in the micromolar range), as expected. In terms of selectivity, compared to previously published rhenium complex-based CA inhibitors, complex 3b showed one of the highest selectivities against hCA IX and hCA XII compared to the off-target isoforms hCA I and hCA II, making it a potential anti-cancer drug candidate. Molecular docking calculations were performed to investigate the inhibition profiles of the investigated compounds at the tumour-associated hCA IX active site and to rationalize our results.

Download Full-text