Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action (original) (raw)
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Phytochemistry Reviews, 2011
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Acquired Immunodeficiency Syndrome (AIDS), which chiefly originatesfroma retrovirus named Human Immunodeficiency Virus (HIV), has impacted about 70 million people worldwide. Even though several advances have been made in the field of antiretroviral combination therapy, HIV is still responsible for a considerable number of deaths in Africa. The current antiretroviral therapies have achieved success in providing instant HIV suppression but with countless undesirable adverse effects. Presently, the biodiversity of the plant kingdom is being explored by several researchers for the discovery of potent anti-HIV drugs with different mechanisms of action. The primary challenge is to afford a treatment that is free from any sort of risk of drug resistance and serious side effects. Hence, there is a strong demand to evaluate drugs derived from plants as well as their derivatives. Several plants, such as Andrographis paniculata, Dioscorea bulbifera, Aegle marmelos, Wistaria floribunda, Lindera chunii, Xanthoceras sorbifolia and others have displayed significant anti-HIV activity. Here, weattempt to summarize the main results, which focus on the structures of most potent plant-based natural products having anti-HIV activity along with their mechanisms of action and IC 50 values, structure-activity-relationships and important key findings.
2020
AIDS, as a lethal disease, is caused by infection with the HIV virus that affects millions of people. Three essential enzymes should be encoded for replication of HIV virus: protease, integrase and reverse transcriptase (RT). RT has two different activities including DNA polymerase and ribonuclease H (RNase H). However, all of the marketed RT inhibitors target only the DNA polymerase activity. Therefore, ribonuclease H activity may serve as a new target for drug discovery. In the present study, a series of 3-Hydroxypyrimidine-2, 4-dione derivatives as potent RT-associated RNase H inhibitors were applied to QSAR analysis. Two methods including multiple linear regressions (MLR) and partial least squared based on genetic algorithm (GA-PLS) were utilized to find the relationship between the structural feathers and inhibitory activities of these compounds. The best multiple linear regression equation was generated by GA-PLS method. A combination of 2D autocorrelations, topological, atom-...
Docking study of HIV-1 reverse transcriptase with phytochemicals
Bioinformation, 2011
Natural products are important sources of drug discovery. In this context groups of different set of phytochemicals were taken and docked into the different cavities of the Reverse transcriptase (PDB ID: 1REV) of Human immunodeficiency virus (HIV) and results were discussed. Natural compounds such as Curcumin, Geranin, Gallotannin, Tiliroside, Kaempferol-3-o-glucoside and Trachelogenin were found to very effective according to its binding energy and ligand efficiency score. Those compounds also were found to have no adverse effect as carcinogenicity and mutagenicity and favorable drug likeness score. Hence, considering the facts those compounds could use effectively for HIV-1 drug discovery.
Design, Synthesis and Biological Evaluation of Novel Galloyl Derivatives as HIV-1 RNase H Inhibitors
Chemical Biology & Drug Design, 2018
Human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated ribonuclease H (RNase H) remains as the only enzyme encoded within the viral genome not targeted by current antiviral drugs. In this work, we report the design, synthesis and biological evaluation of a novel series of galloyl derivatives with HIV-1 RNase H inhibitory activity. Most of them showed IC 50 s at sub to low micromolar concentrations in enzymatic assays. The most potent compound was II-25 that showed an IC 50 of 0.72 ± 0.07 μM in RNase H inhibition assays carried out with the HIV-1 BH10 RT. II-25 was 2.8 times more potent than β-thujaplicinol in these assays. Interestingly, II-25 and other galloyl derivatives were also found to inhibit the HIV IN strand transfer activity in vitro. Structure-activity relationships (SAR) studies and molecular modeling analysis predict key interactions with RT residues His539 and Arg557, while providing helpful insight for further optimization of selected compounds.
International Journal of Applied Pharmaceutics, 2024
Objective: This study aims to predict the active compound of Moringa oleifera for the treatment of Human Immunodeficiency Virus (HIV), specifically targeting the HIV-1 reverse transcriptase (HIV-1 RT) enzyme using network pharmacology and molecular docking approach. Methods: The active ingredients of M. oleifera, were screened from the Knapsack database. Subsequently, HIV-1 RT and its related target compounds were retrieved from the Genecard database. The analysis of common targets involved protein-protein interactions (PPI) analysis using string databases and constructing interaction IDs using Cytoscape software. Gene Ontology (GO) functional and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Molecular docking studies were conducted using AutoDock Vina software to validate the results of the network pharmacological analysis. Results: A total of 63 active ingredients and 8601 targets related to HIV-1 RT were identified. The network analysis, encompassing GO and KEGG enrichment, revealed strong associations of common targets with key signaling pathways such as Tumor Necrosis Factor (TNF), Toll-Like Receptor (TLR), and apoptosis. Additionally, 11 compounds of M. oleifera, including apigenin, benzyl isothiocyanate, benzylamine, caffeic acid, ferulic acid, epicatechin, kaempferol, gallic acid, luteolin, syringic acid and vanillin were identified as potential vital compounds. Molecular docking analysis highlighted apigenin and kaempferol as the most promising compounds, exhibiting the lowest binding affinity to the HIV-1 RT enzyme. These compounds correlated with caspase-3(CASP3), caspase-9 (CASP9), and BCL2 Apoptosis Regulator (BAX) protein, stimulating cell apoptosis through multiple pathways. Conclusion: The study highlighted that apigenin and kaempferol are potential compound of M. oleifera in HIV-1 treatment through inhibition activity at HIV-1 RT Enzyme.