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.