Current Signal Transduction Therapy - Volume 20, Issue 1, 2025

HIV/AIDS remains a global health challenge, demanding innovative antiretroviral strategies. HIV integrase inhibition, a promising therapeutic target, warrants exploration. This study investigates the potential of Cryptolepine and analogues as integrase inhibitors through in-silico docking and ADMET profiles. Docking simulations reveal binding affinities, guiding rational drug design. ADMET predictions assess the pharmacokinetics, ensuring clinical viability. Cryptolepine and analogues show promise, offering a pathway for therapeutic development against HIV/AIDS. Further, insights contribute to ongoing efforts in combating the pandemic with effective antiretroviral strategies.

Molecular docking investigations utilized Molegro Virtual Docker (MVD) 6.0, with the target protein [PDB ID: 1QS4] obtained from the Protein Data Bank. Ligands, particularly Cryptolepine-based, were selected from PubChem with adherence to Lipinski's Rule of Five for drug-like properties. Computational tools, including pkCSM, aided ADMET profiling. This study, conducted on an AMD Ryzen 3 3200U computer with Windows 10 home, enhances understanding and potential therapeutic strategies against HIV/AIDS.

From a virtual screening of the PubChem database, the top ten candidates were selected based on their MolDock scores against the target 1QS4. All compounds had MolDock scores greater than -70.00 kcal, with [01] RPA 1 exhibiting the highest MolDock Score (-83.85 kcal) and Rerank Score (-39.59 kcal). These compounds possessed the essential pharmacophore for HIV integrase inhibition against 1QS4. However, three compounds, including [01] RPA 1, [00] RPA 1_6, and [04] RPA 1_1, showed no hydrogen bonding interactions with Val 79 and Val 150 amino acid residues. This highlights the importance of structural analysis in understanding ligand-receptor interactions for rational drug design against HIV integrase.

This study investigates how Cryptolepine analogues inhibit HIV integrase via docking and ADMET analysis. All analogues exhibit strong binding, especially those within the 400-500 Da range. Specific amino acids and hydrogen bonds influence interactions. Compound [01] RPA 1_3 shows high intestinal absorption and promising properties, making it a potential HIV integrase inhibitor. The study highlights the importance of a comprehensive ADMET profile in drug development and suggests further exploration of [01] RPA 1_3 for HIV/AIDS therapy.

Peroxisome Proliferator-Activated Receptors (PPARs) are nuclear receptors involved in the regulation of glucose and lipid metabolism, making them potential targets for treating type 2 diabetes mellitus. 5-Benzylthiazolidine-2, 4-dione derivatives, organic compounds with a thiazolidine-2, 4-dione core and a benzyl moiety at the 5-position, have garnered attention for their diverse pharmacological activities, including anti-inflammatory, anti-cancer, anti-diabetic, anti-tubercular, and anti-viral properties.

This research aimed to identify 5-benzylthiazolidine-2,4-dione derivatives as synthetic PPAR-gamma agonists using computational methods, such as molecular docking and in silico ADMET analysis. Virtual screening generated potential molecules, and molecular docking studies using AutoDock Vina 1.5.6 were performed at the active site of the PPAR-gamma receptor (PDBID: 4PRG).

Nine hits were identified based on their binding affinities and were further evaluated using SwissADME for their ADME properties. These nine compounds demonstrated superior ADME profiles and bioavailability compared to the standard drug Rosiglitazone.

This study provides a comprehensive computational approach for discovering novel PPAR-gamma receptor agonists, potentially advancing experimental diabetes research.