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image of Synthesis of Novel Indolyl Aryl Sulfone-clubbed Hydrazone Derivatives as Potential HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: Molecular Modeling and QSAR Studies

Abstract

Background

Non-Nucleoside Reverse Transcriptases Inhibitors (NNRTIs) are among the most extensively studied enzymes for understanding the biology of Human Immunodeficiency Viruses (HIV) and designing inhibitors for managing HIV infections. Indolyl aryl sulfones (IASs), an underexplored class of potent NNRTIs, require further exploration for the development of newer drugs for HIV.

Aims

In this context, we synthesized a series of novels by Indolyl Aryl Sulfones with a hydrazone moiety at the carboxylate site of the indole nucleus. A 2D-QSAR model was developed to predict Reverse Transcriptase inhibitory activity against wild-type RT (WT-RT) enzyme.

Method

The model was successfully applied to predict the HIV-1 inhibitory activity of known Indolyl Aryl Sulfones. Considering the reliability, robustness, and reproducibility of the 2D-QSAR model, we made an prediction of the RT inhibition for our synthesized compounds (-).

Results

Molecular docking and dynamics simulations established our synthesized Indolyl Aryl Sulfones, particularly compounds , and , as effective NNRTIs by stabilizing HIV reverse transcriptase's structure. Binding energy calculations revealed compound as the strongest inhibitor (-43.21 ± 0.09 kcal/mol), followed by (-40.94 ± 0.10 kcal/mol) and (-39.18±0.08 kcal/mol), emphasizing their binding affinity towards HIV reverse transcriptase.

Conclusion

In summary, the synthesized Indolyl Aryl Sulfones, particularly compounds , , and , demonstrate significant potential as Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) against HIV. These results highlight the promising role of these compounds in developing novel NNRTIs for managing HIV infections.

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2024-10-14
2024-11-26

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/content/journals/cmc/10.2174/0109298673318987240926052450
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Synthesis of Novel Indolyl Aryl Sulfone-clubbed Hydrazone Derivatives as Potential HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: Molecular Modeling and QSAR Studies
Bentham Science Publishers ; https://doi.org/10.2174/0109298673318987240926052450
/content/journals/cmc/10.2174/0109298673318987240926052450
/content/journals/cmc/10.2174/0109298673318987240926052450
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  • Article Type:     Research Article
Keywords: Indolyl aryl sulfones ; HIV ; molecular dynamic simulations ; 2D-QSAR ; molecular docking ; NNRT inhibition

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