CoMFA and CoMSIA 3D-QSAR studies on quionolone caroxylic acid derivatives inhibitors of HIV-1 integrase

Background: S-dihydro-alkyloxy-benzyl-oxopyrimidines (S-DABOs) as non-nucleoside reverse transcriptase inhibitors have received considerable attention during the last decade due to their high potency against HIV-1. Methods: In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR) of a series of 38 S-DABO analogues developed in our lab was studied using Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). The Docking/MMFF94s computational protocol based on the co-crystallized complex (PDB ID: 1RT2) was used to determine the most probable binding mode and to obtain reliable conformations for molecular alignment. Statistically significant CoMFA (q2=0.766 and r2=0.949) and CoMSIA (q2=0.827 and r2=0.974) models were generated using the training set of 30 compounds on the basis of hybrid docking-based and ligand-based alignment. Results: The predictive ability of CoMFA and CoMSIA models was further validated using a test set of eight compounds with predictive r2 pred values of 0.843 and 0.723, respectively. Conclusion: The information obtained from the 3D contour maps can be used in designing new SDABO derivatives with improved HIV-1 inhibitory activity.

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Computational Studies of 3D-QSAR on a Highly Active Series of Naturally Occurring Nonnucleoside Inhibitors of HIV-1 RT (NNRTI)

Journal of Computational Biophysics and Chemistry ◽

10.1142/s2737416520500362 ◽

2020 ◽

pp. 2050036

Author(s):

Waqar Hussain ◽

Arshia Majeed ◽

Ammara Akhtar ◽

Nouman Rasool

Keyword(s):

Three Dimensional ◽

3D Qsar ◽

Qsar Modeling ◽

Qsar Analysis ◽

Qsar Studies ◽

Highly Active ◽

Naturally Occurring ◽

Zinc Database ◽

Immunodeficiency Syndrome ◽

Hiv 1

HIV is one of the deadliest viruses in the history of mankind, it is the root cause of Acquired Immunodeficiency Syndrome (AIDS) around the world. Despite the fact that the antiviral therapy used against HIV-1 infection is effective, there is also rapidly growing cases of drug resistance in the infected patient along with different severe side effects. Therefore, it is of dire and immediate need to find novel inhibitors against HIV-1 Reverse Transcriptase (RT). In this study, the potential of naturally occurring compounds extracted from plants has been studied with the help of Three-Dimensional-Quantitative Structure–Activity Relationships (3D-QSAR) analysis. A total of 20 compounds, retrieved from a ZINC database, were analyzed with the help of 3D-QSAR to identify a potential inhibitor of HIV-1 RT. By evaluation of seven models generated with the help of MIF analysis and 3D-QSAR modeling, compound 3 (ZINC ID: ZINC20759448) was observed to outperform others by showing optimal results in QSAR studies. This compound has also been biologically validated by a recently reported previous study. Thus, this compound can be used as a potential drug against infection caused by HIV-1, specifically AIDS.

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Synthesis, biological evaluation and 3D-QSAR studies of 3-keto salicylic acid chalcones and related amides as novel HIV-1 integrase inhibitors

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2011.01.047 ◽

2011 ◽

Vol 19 (6) ◽

pp. 2030-2045 ◽

Cited By ~ 58

Author(s):

Horrick Sharma ◽

Shivaputra Patil ◽

Tino W. Sanchez ◽

Nouri Neamati ◽

Raymond F. Schinazi ◽

...

Keyword(s):

Salicylic Acid ◽

3D Qsar ◽

Biological Evaluation ◽

Integrase Inhibitors ◽

Qsar Studies ◽

Hiv 1

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Molecular docking and 3D-QSAR studies on triazolinone and pyridazinone, non-nucleoside inhibitor of HIV-1 reverse transcriptase

Journal of Molecular Modeling ◽

10.1007/s00894-009-0625-8 ◽

2009 ◽

Vol 16 (6) ◽

pp. 1169-1178 ◽

Cited By ~ 29

Author(s):

Sree Kanth Sivan ◽

Vijjulatha Manga

Keyword(s):

Molecular Docking ◽

Reverse Transcriptase ◽

3D Qsar ◽

Qsar Studies ◽

Hiv 1

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Combination of 2D and 3D-QSAR studies on DAPY and DANA derivatives as potent HIV-1 NNRTIs

Journal of Molecular Structure ◽

10.1016/j.molstruc.2021.131603 ◽

2022 ◽

Vol 1249 ◽

pp. 131603

Author(s):

Xiao Ding ◽

Dongwei Kang ◽

Lin Sun ◽

Peng Zhan ◽

Xinyong Liu

Keyword(s):

3D Qsar ◽

Qsar Studies ◽

2D And 3D ◽

Hiv 1

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3D-QSAR studies on chromone derivatives as HIV-1 protease inhibitors

Journal of Molecular Structure ◽

10.1016/j.molstruc.2003.10.036 ◽

2004 ◽

Vol 689 (1-2) ◽

pp. 99-106 ◽

Cited By ~ 23

Author(s):

Jiraporn Ungwitayatorn ◽

Weerasak Samee ◽

Jutarat Pimthon

Keyword(s):

Protease Inhibitors ◽

3D Qsar ◽

Qsar Studies ◽

Chromone Derivatives ◽

Hiv 1

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3D-QSAR studies on 5-hydroxy-6-oxo-1,6-dihydropyrimidine-4- carboxamide derivatives as HIV-1 integrase inhibitors

Journal of the Taiwan Institute of Chemical Engineers ◽

10.1016/j.jtice.2015.07.024 ◽

2016 ◽

Vol 59 ◽

pp. 61-68 ◽

Cited By ~ 13

Author(s):

Saloni Patel ◽

Bhumika Patel ◽

Hardik Bhatt

Keyword(s):

3D Qsar ◽

Integrase Inhibitors ◽

Qsar Studies ◽

Hiv 1

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Virtual Screening, Biological Evaluation, and 3D-QSAR Studies of New HIV-1 Entry Inhibitors That Function via the CD4 Primary Receptor

Molecules ◽

10.3390/molecules23113036 ◽

2018 ◽

Vol 23 (11) ◽

pp. 3036 ◽

Cited By ~ 5

Author(s):

Chaozai Zhang ◽

Huijun Zhang ◽

Lina S. Huang ◽

Siyu Zhu ◽

Yan Xu ◽

...

Keyword(s):

Biological Activities ◽

Similarity Index ◽

3D Qsar ◽

Biological Evaluation ◽

Rational Drug Design ◽

Field Analysis ◽

Qsar Studies ◽

Entry Inhibitors ◽

Primary Receptor ◽

Hiv 1

Human immunodeficiency virus type 1 (HIV-1) is responsible for the majority of HIV infections worldwide, and we still lack a cure for this infection. Blocking the interaction of HIV-1 and its primary receptor CD4 is one strategy for identifying new anti-HIV-1 entry inhibitors. Here we report the discovery of a novel ligand that can inhibit HIV-1 entry and infection via CD4. Biological and computational analyses of this inhibitor and its analogs, using bioactivity evaluation, Rule of Five (RO5), comparative molecular field analysis (CoMFA)/comparative molecular similarity index analysis (CoMSIA) models, and three-dimensional quantitative structure-activity relationship (3D-QSAR), singled out compound 3 as a promising lead molecule for the further development of therapeutics targeting HIV-1 entry. Our study demonstrates an effective approach for employing structure-based, rational drug design techniques to identify novel antiviral compounds with interesting biological activities.

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