Identification of Luteolin and Some Other Phenolics of Propolis as HIV-1-reverse Transcriptase Inhibitors

Abstract

The inhibitory effects of Anatolian propolis were investigated against Human Immunodeficiency Virus type-1 reverse transcriptase (HIV-1 RT). The aim of the study was to assess the antiviral properties of the water-soluble propolis extract and to identify naturally occurring inhibitors within this type of propolis, with a specific focus on compounds demonstrating non-cytotoxic antiviral activity. To accomplish this, propolis extract’s antioxidant capacities (FRAP), radical scavenging activities, total flavonoids (TFC), and phenolic contents (TPC) were determined and found to be 1088.67 ± 43.30 (μmol FeSO₄∙7H₂O/g), 3.19 ± 0.11 mg/mL, 1.05 ± 0.1 (mg QE/g) and 56.31 ± 0.40 mg GAE/g), respectively. The content of the 2-kDa filtrate of extract was identified by the Orbitrap LC-MS, RP-HPLC-UV, HPLC-DAD. HIV-1 RT inhibition assays were performed for identified phenolic compounds, with dioxygen antibody for colorimetric detection and IC₅₀ values were determined against HIV-1 RT. The compounds (pinocembrin, luteolin, myricetin, quercetin, tannic acid, fisetin) with IC₅₀ values below 1 mM have shown a generally synergistic inhibitory effect in their binary combinations at IC₅₀ concentrations. Their combination exhibited an inhibitory effect equivalent to that in positive control presented by Nevirapine. The cytotoxic effects of the most effective 6 phenolic compounds were determined on Jurkat cells by 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay. This observation suggests that these compounds are suitable and promising candidates as potential raw materials for the development of anti-HIV-1 drugs.