MOLECULAR DYNAMICS, DOCKING, DENSITY FUNCTIONAL, AND ADMET STUDIES OF HIV-1 REVERSE TRANSCRIPTASE INHIBITORS

2006 ◽  
Vol 05 (03) ◽  
pp. 579-586 ◽  
Author(s):  
CARLOS H. T. P. DA SILVA ◽  
IVONE CARVALHO ◽  
CARLTON A. TAFT
Keyword(s):  
Molecular Dynamics ◽  
Reverse Transcriptase ◽  
Active Site ◽  
Density Functional ◽  
Docking Studies ◽  
Reverse Transcriptase Inhibitors ◽  
Hydrogen Bond Interaction ◽  
Receptor Interactions ◽  
Similar Mode ◽  
Hiv 1

Molecular dynamics, density functional with correlation, as well as docking studies of inhibitors of HIV-1 reverse transcriptase (RT) are reported. We propose in this work a novel potential HIV-1 RT inhibitor (RTI), which theoretically appears to bind in a similar mode as other nucleoside reverse transcriptase inhibitors, and in addition, it introduces a new hydrogen bond interaction with Trp229. Our novel RTI has high docking scores and the molecular dynamics studies, as well as the analysis of the ligand-receptor interactions in the active site and the ADMET properties suggest advantages and specificities for this potential RTI.

Acylthiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors: docking studies and ligand-based CoMFA and CoMSIA analyses

2009 ◽  
Vol 15 (7) ◽  
pp. 871-884 ◽  
Author(s):  
Elena Cichero ◽  
Sara Cesarini ◽  
Andrea Spallarossa ◽  
Luisa Mosti ◽  
Paola Fossa
Keyword(s):  
Reverse Transcriptase ◽  
Docking Studies ◽  
Reverse Transcriptase Inhibitors ◽  
Hiv 1

QSAR and Docking Studies of DATA Analogues as HIV-1 Reverse Transcriptase Inhibitors

2018 ◽  
Vol 16 (2) ◽  
pp. 153-159 ◽  
Author(s):  
Jianbo Tong ◽  
Shan Lei ◽  
Pei Zhan ◽  
Shangshang Qin ◽  
Yang Wang
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Reverse Transcriptase ◽  
3D Qsar ◽  
Docking Studies ◽  
Reverse Transcriptase Inhibitors ◽  
Electronic Density ◽  
Topomer Comfa ◽  
Rt Inhibitors ◽  
Hiv 1

Background: Acquired Immunodeficiency Syndrome (AIDS) caused by Human Immunodeficiency Virus (HIV) has seriously threatened human health, so development of new, selective and safe non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) remains a high priority for medical research. Diaryltriazine (DATA) have been identified as a new class of potent nonnucleoside HIV-1 Reverse Transcriptase (RT) inhibitors. The study deals with Topomer CoMFA (Comparative Molecular Field Analysis) and molecular docking to explore the important features of DATA analogues for exerting potent HIV-1 RT inhibitors activity. Methods: In this work, 40 DATA analogues were studied using a combination of molecular modeling techniques including Three-Dimensional Quantitative Structure–Activity Relationship (3D-QSAR), molecular docking, and Topomer CoMFA were used to build 3D-QSAR models. Results: The results show that the Topomer CoMFA analysis has the cross-validation q2 = 0.800, SDCV = 0.45, the non-cross-validated r2 = 0.958, SD = 0.21, and the correlation coefficient of external validation Q2 ext = 0.965 showed that the model is reasonable and credible, and has a good predictive ability. Then binding mode pattern of the compounds to the binding site of enzyme was confirmed and the mechanism of drug and acceptor was studied by docking studies, the results showed that the drug and GLU138, LYS101, THR139 sites have an obvious function, these researches have provided an useful information for designing more effective HIV-1IN inhibitors. Conclusion: A series of 40 DATAs analogues was subjected to a 3D-QSAR study. Using Topomer CoMFA 3D-QSAR method built model, and the model has shown a good predictive and statistical validation. Substituent with low electronic density in the R5 and R3 positions and substituent with high electronic density in the R2 and C2 positions will increase the biological activity, small substituent on R4 positions and naphthyloxy as the spacer group C6 substituent hydrophobic will increase biological activity. This effect is supported by Topomer CoMFA contour map and docking results of HIV-1RT inhibition active site, the results of the 3D-QSAR and docking analyses have provided a guide for the synthesis of new putative inhibitors for HIV-1RT to improved inhibitory activity.

Molecular Docking Studies and Synthesis of Amino-oxy-diarylquinoline Derivatives as Potent Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors

Drug Research ◽  
2019 ◽  
Vol 69 (12) ◽  
pp. 671-682 ◽  
Author(s):  
Arthit Makarasen ◽  
Mayuso Kuno ◽  
Suwicha Patnin ◽  
Nanthawan Reukngam ◽  
Panita Khlaychan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Reverse Transcriptase ◽  
Lymphoblastic Leukemia ◽  
Docking Studies ◽  
Elisa Method ◽  
Reverse Transcriptase Inhibitors ◽  
Anti Hiv Agents ◽  
Near Future ◽  
Anti Hiv ◽  
Hiv 1

AbstractIn this study, amino-oxy-diarylquinolines were designed using structure-guided molecular hybridization strategy and fusing of the pharmacophore templates of nevirapine (NVP), efavirenz (EFV), etravirine (ETV, TMC125) and rilpivirine (RPV, TMC278). The anti-HIV-1 reverse transcriptase (RT) activity was evaluated using standard ELISA method, and the cytotoxic activity was performed using MTT and XTT assays. The primary bioassay results indicated that 2-amino-4-oxy-diarylquinolines possess moderate inhibitory properties against HIV-1 RT. Molecular docking results showed that 2-amino-4-oxy-diarylquinolines 8(a-d) interacted with the Lys101 and His235 residue though hydrogen bonding and interacted with Tyr318 residue though π-π stacking in HIV-1 RT. Furthermore, 8a and 8d were the most potent anti-HIV agents among the designed and synthesized compounds, and their inhibition rates were 34.0% and 39.7% at 1 µM concentration. Interestingly, 8a was highly cytotoxicity against MOLT-3 (acute lymphoblastic leukemia), with an IC50 of 4.63±0.62 µg/mL, which was similar with that in EFV and TMC278 (IC50 7.76±0.37 and 1.57±0.20 µg/ml, respectively). Therefore, these analogs of the synthesized compounds can serve as excellent bases for the development of new anti-HIV-1 agents in the near future.

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