Evaluation of antitrichomonal activity of coffeewaste compounds against different Trichomonas vaginalis strains: An in vitro and in silico study.

Trichomoniasis is a Sexually Transmitted Infection (STI) caused by the protozoan Trichomonas vaginalis, closely related to secondary viral infections that have a high impact in the public health costs. Nitroimidazole drugs are the only available treatment options. Thus, refractory cases have emerged in recent years, leading to the necessity of therapeutic alternatives. The use of coffee by-products such as pulp, husks and leaves may represent a sustainable alternative for treatment. The aim of the study was to evaluate the trichomonacidal activity in vitro and in silico of compounds commonly isolated from coffee waste. For this, caffeine, chlorogenic acid, quinic acid, caffeic acid, and mangiferin were tested in vitro for their anti-T. vaginalis activities against strains CDC085 and JT. Transmission electron microscopy (TEM) and molecular docking were performed to unravel a possible mechanism of action. Cytotoxicity in vitro was performed against HeLa cells and vaginal microbiome bacterial isolate, Lactobacillus jensenii. Caffeine, chlorogenic acid, and quinic acid presented potent activity against CDC085 strain of T. vaginalis, with IC50 of 4.83 μM, 10.01 μM, and 12.73 μM, respectively. TEM showed alterations in trophozoites hydrogenosomes for both organic acids treatments and autophagy process when treated with caffeine. The compounds had no inhibitory effect against the JT strain. Quinic acid revealed promising interactions with parasite's lactate dehydrogenase (LDH) through in silico molecular docking. The three promising compounds did not show cytotoxicity against HeLa cells (selectivity index > 10) nor against bacteria from the vaginal microbiota (MIC>400 μM). Our findings have pointed caffeine and quinic acid as potent anti-T. vaginalis agents, with impactful IC50 values and primarily safe against HeLa and L. jensenii cells. Their exact mechanism of action still remains unclear, although TEM and molecular docking results may orientate next steps regarding autophagy alterations and LDH interaction, respectively. We highlight that coffee-derived compounds should be considered as drug candidates for trichomoniasis, presenting promising agents with potential for further preclinical evaluation.