BIOMAT Database Logo BIOMAT Database Logo

In silico design, synthesis and anti-HIV activity of quinoline derivatives as non-nucleoside reverse transcriptase inhibitors (NNRTIs). 2022

Vishal K Singh, and Richa Mishra, and Priyanka Kumari, and Anup Som, and Aditya K Yadav, and Nand K Ram, and Pradeep Kumar, and Dominique Schols, and Ramendra K Singh
Bioorganic Research Laboratory, Department of Chemistry, University of Allahabad, Prayagraj 211002, India.

A series of quinoline derivatives has been designed, synthesized and screened for their anti-HIV properties. The drug-like properties of compounds were evaluated first and then molecular docking using DS v20.1.0.19295 software showed that the compounds behaved as non-nucleoside reverse transcriptase inhibitors (NNRTIs) while interacting at the allosteric site of target HIV-RT protein (PDB:3MEC). The docking results revealed that all compounds formed hydrogen bonds with Lys101, Lys103, Val179, Tyr188, Gln190, Gly190, Pro225, Phe227, and Tyr318, and showed π-interaction with Tyr188 and Tyr318. TOPKAT (Toxicity Prediction by Komputer Assisted Technology) results confirmed that the compounds were found to be less toxic than the reference drugs. Density functional theory (DFT) analysis was performed to assess the binding affinity of all compounds. Further, molecular dynamics (MD) simulations were performed on compound 6 and delavirdine with HIV-RT enzyme. Comprehensive MD analyses showed a similar pattern of conformational stability and flexibility in both the complexes suggesting alike inhibitory action. The hydrogen-bonding interactions and the binding energy of active-site residues for the compound 6 complex revealed strong inhibitory activity than the reference (delavirdine) complex. Thus, the compound 6 might act as a potential inhibitor against HIV-RT. Overall, this study revealed that compound 6 (5-hydroxy-N-(4-methyl-2-oxo-1,2-dihydroquinolin-8-yl) thiophene-2-sulfonamide) has prudent anti-HIV activity against both HIV-1 (SI = 2.65) and HIV-2 (SI = 2.32) that can further be utilised in drug discovery against HIV virus.

UI MeSH Term Description Entries
D011804 Quinolines
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human
D054303 HIV Reverse Transcriptase A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process. Reverse Transcriptase, HIV,Reverse Transcriptase, Human Immunodeficiency Virus,Transcriptase, HIV Reverse
D062105 Molecular Docking Simulation A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein. Molecular Docking,Molecular Docking Simulations,Molecular Docking Analysis,Analysis, Molecular Docking,Docking Analysis, Molecular,Docking Simulation, Molecular,Docking, Molecular,Molecular Docking Analyses,Molecular Dockings,Simulation, Molecular Docking
D018894 Reverse Transcriptase Inhibitors Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. Reverse Transcriptase Inhibitor,Inhibitors, Reverse Transcriptase,Inhibitor, Reverse Transcriptase,Transcriptase Inhibitor, Reverse
D020008 Delavirdine A potent, non-nucleoside reverse transcriptase inhibitor with activity specific for HIV-1. Delavirdine Mesylate,Rescriptor,U-90152,U-90152S,Mesylate, Delavirdine,U 90152,U 90152S,U90152,U90152S
D020134 Catalytic Domain The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. Active Site,Catalytic Core,Catalytic Region,Catalytic Site,Catalytic Subunit,Reactive Site,Active Sites,Catalytic Cores,Catalytic Domains,Catalytic Regions,Catalytic Sites,Catalytic Subunits,Core, Catalytic,Cores, Catalytic,Domain, Catalytic,Domains, Catalytic,Reactive Sites,Region, Catalytic,Regions, Catalytic,Site, Active,Site, Catalytic,Site, Reactive,Sites, Active,Sites, Catalytic,Sites, Reactive,Subunit, Catalytic,Subunits, Catalytic

Related Publications

Vishal K Singh, and Richa Mishra, and Priyanka Kumari, and Anup Som, and Aditya K Yadav, and Nand K Ram, and Pradeep Kumar, and Dominique Schols, and Ramendra K Singh
Synthesis and molecular docking studies of quinoline derivatives as HIV non-nucleoside reverse transcriptase inhibitors.
January 2020, Turkish journal of chemistry,
Vishal K Singh, and Richa Mishra, and Priyanka Kumari, and Anup Som, and Aditya K Yadav, and Nand K Ram, and Pradeep Kumar, and Dominique Schols, and Ramendra K Singh
[Progress in HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs)].
August 2004, Yao xue xue bao = Acta pharmaceutica Sinica,
Vishal K Singh, and Richa Mishra, and Priyanka Kumari, and Anup Som, and Aditya K Yadav, and Nand K Ram, and Pradeep Kumar, and Dominique Schols, and Ramendra K Singh
Fullerene Derivatives of Nucleoside HIV Reverse Transcriptase Inhibitors-In Silico Activity Prediction.
October 2018, International journal of molecular sciences,
Vishal K Singh, and Richa Mishra, and Priyanka Kumari, and Anup Som, and Aditya K Yadav, and Nand K Ram, and Pradeep Kumar, and Dominique Schols, and Ramendra K Singh
Novel indole-3-sulfonamides as potent HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs).
January 2008, Bioorganic & medicinal chemistry letters,
Vishal K Singh, and Richa Mishra, and Priyanka Kumari, and Anup Som, and Aditya K Yadav, and Nand K Ram, and Pradeep Kumar, and Dominique Schols, and Ramendra K Singh
Synthesis and anti-HIV activity of new alkenyldiarylmethane (ADAM) non-nucleoside reverse transcriptase inhibitors (NNRTIs) incorporating benzoxazolone and benzisoxazole rings.
April 2006, Bioorganic & medicinal chemistry,
Vishal K Singh, and Richa Mishra, and Priyanka Kumari, and Anup Som, and Aditya K Yadav, and Nand K Ram, and Pradeep Kumar, and Dominique Schols, and Ramendra K Singh
Strategies in the Design and Development of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs).
September 2023, Viruses,
Vishal K Singh, and Richa Mishra, and Priyanka Kumari, and Anup Som, and Aditya K Yadav, and Nand K Ram, and Pradeep Kumar, and Dominique Schols, and Ramendra K Singh
[Design, synthesis and biologic evaluation of diarylbenzimidazole derivatives as novel HIV-1 non-nucleoside reverse transcriptase inhibitors].
November 2009, Yao xue xue bao = Acta pharmaceutica Sinica,
Vishal K Singh, and Richa Mishra, and Priyanka Kumari, and Anup Som, and Aditya K Yadav, and Nand K Ram, and Pradeep Kumar, and Dominique Schols, and Ramendra K Singh
Synthesis of 2-methylsulfanyl-1H-imidazoles as novel non-nucleoside reverse transcriptase inhibitors (NNRTIs).
June 2003, Archiv der Pharmazie,
Vishal K Singh, and Richa Mishra, and Priyanka Kumari, and Anup Som, and Aditya K Yadav, and Nand K Ram, and Pradeep Kumar, and Dominique Schols, and Ramendra K Singh
Current and emerging non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV-1 treatment.
October 2019, Expert opinion on drug metabolism & toxicology,
Vishal K Singh, and Richa Mishra, and Priyanka Kumari, and Anup Som, and Aditya K Yadav, and Nand K Ram, and Pradeep Kumar, and Dominique Schols, and Ramendra K Singh
Design, synthesis, anti-HIV evaluation and molecular modeling of piperidine-linked amino-triazine derivatives as potent non-nucleoside reverse transcriptase inhibitors.
June 2012, Bioorganic & medicinal chemistry,
Copied contents to your clipboard!