Discovery of thienopyrimidine analog G-18 as a novel anti-trichomonal agent
TL;DR
G-18 is supported as a promising anti-trichomonal lead compound with rapid in vitro activity and a preliminary selectivity profile under the tested conditions, and limited cytotoxicity towards mammalian cells under the tested conditions.
Abstract
Trichomoniasis, caused by Trichomonas vaginalis, is the most prevalent nonviral sexually transmitted infection worldwide. The occurrence of treatment failure with metronidazole (MTZ) and the adverse effects of currently available nitroimidazoles underscore the necessity for novel therapeutic candidates. From a library of synthetic thienopyrimidine derivatives, G-18 was identified as a lead compound. G-18 exhibited potent anti-T. vaginalis activity against the tested T. vaginalis isolate, with a minimum inhibitory concentration (MIC) of 4 μg/mL and a half-maximal inhibitory concentration (IC50) of 1 μg/mL at 24 h, and it significantly reduced trophozoite viability within 2 h. Flow cytometry confirmed a higher proportion of propidium iodide (PI)-positive parasites following G-18 treatment compared to MTZ treatment (51.2% vs. 10.4%). G-18 demonstrated limited cytotoxicity towards mammalian cells under the tested conditions. Scanning and transmission electron microscopy revealed pronounced ultrastructural damage, including surface roughening, membrane disruption, and organelle disorganization. These findings support G-18 as a promising anti-trichomonal lead compound with rapid in vitro activity and a preliminary selectivity profile under the tested conditions.