title: High-throughput virtual screening of phloroglucinol derivatives against HIV-reverse transcriptase.
abstract: Therapeutic agents exert their pharmacological and adverse effects by interacting with molecular targets. Even if drug molecules are intended to interact with specific targets in a desirable manner, they are often found to bind to other targets. Nowadays, research is focused on a single molecule that simultaneously targets multiple disease-causing proteins. Therefore, off-target identification of existing chemical space can be a valuable tool to find safe and effective multi-targeted therapeutic agents at a significantly lower cost to patients. Phloroglucinols represent a class of compounds, which exhibits a diverse range of biological activities, such as anti-HIV, antimalarial, antileishmanial, antituberculosis, antibacterial, and antifungal. The aim of the current study is to explore untapped potential of various series of phloroglucinols against HIV reverse transcriptase (HIV-RTase). A series of filtering parameters was applied in search of viable phloroglucinol derivatives against HIV-RTase. A library of phloroglucinol derivatives was screened based on their toxicity potential followed by predicted ADME parameters. The filtered compounds were then carried forward for docking analysis against HIV-RTase. A set of 37 phloroglucinol compounds with diverse pharmacological profile was found to have good binding affinity towards HIV-RTase. These molecules formed hydrogen bonds with Lys101, Lys103, Val106, and Leu234 residues and π–π stacking interaction with Tyr318 residue of the protein. Here, we propose potential phloroglucinol derivatives with different known biological activity that can be repurposed as potential hits against HIV.
authors: Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sect-67, SAS Nagar, 160062 Punjab, India.
authors: Vilas
authors: V
authors: Belekar
authors: Anup
authors: A
authors: Shah
authors: Prabha
authors: P
authors: Garg
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D015195:Drug Design; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D057166:High-Throughput Screening Assays; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D010696:Phloroglucinol / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology; D011485:Protein Binding; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D010696:Phloroglucinol; D054303:HIV Reverse Transcriptase