Hazrat Ali, Abdul Latif, Mumtaz Ali, Ammara, Muhammad Waqas, Manzoor Ahmad, Asaad Khalid, Ajmal Khan, Ahmed Al-Harrasi
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引用次数: 0
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 in-silico prediction of the RT inhibition for our synthesized compounds (1-14).
Results: Molecular docking and dynamics simulations established our synthesized Indolyl Aryl Sulfones, particularly compounds 23, 24, and 28, as effective NNRTIs by stabilizing HIV reverse transcriptase's structure. Binding energy calculations revealed compound 28 as the strongest inhibitor (-43.21 ± 0.09 kcal/mol), followed by 23 (-40.94 ± 0.10 kcal/mol) and 24 (-39.18±0.08 kcal/mol), emphasizing their binding affinity towards HIV reverse transcriptase.
Conclusion: In summary, the synthesized Indolyl Aryl Sulfones, particularly compounds 23, 24, and 28, 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.
期刊介绍:
Aims & Scope
Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.