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.

Arylsulfone-Based HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors

“…Currently, Arylsulfone-based HIV-1 non-nucleoside reverse transcriptase inhibitors there is a rich availability of anti retroviral drugs for the treatment of initial HIV infection (SupplementaRy table 1) [20] . Beside the recently approved etravirine and rilpivirine [21], many other new NNRTIs have been recently described that look promising in terms of their potency and resistance profile (e.g., MK-1439 [22] and Lersivirine [23]). …”

Phloroglucinol and Its Derivatives: Antimicrobial Properties toward Microbial Pathogens

“…Because of their antibacterial, antiviral, antifungal, antimalarial, and antileishmanial properties, numerous phloroglucinols have been recognized as multitarget therapeutic drugs. 160 As a result, it would be worthwhile to investigate and test possible phloroglucinol derivatives using a computational method such as molecular docking. 161 Molecular docking has been widely acknowledged as a method for drug design and development.…”

“…162 High-throughput virtual screening of numerous possible phloroglucinol derivatives that can be used to treat microbial infection can be performed using molecular docking as an alternate strategy. 160 Several computational tools have been developed for virtual drug screening. 162 PG and its derivatives (Supporting Information Table S1) can be employed as a framework for developing a potent chemical molecule with broad-spectrum antimicrobial activity against microbial infections in silico.…”

Myrtucomvalones A–C, three unusual triketone–sesquiterpene adducts from the leaves of Myrtus communis ‘Variegata’

“…20,21 Thus, the antiviral effects of compounds 1-7 against respiratory syncytial virus (RSV) were evaluated in HEp-2 cells using the cytopathic effect (CPE) reduction assay. Compounds 3, 5, and 7 exhibited moderate inhibitory activities against RSV A2 strain with IC 50 values ranging from 11.67 AE 0.95 to 15.85 AE 3.02 mM, while the IC 50 value of the positive control ribavirin was 10.20 AE 0.90 mM.…”