Análogos monocarbonílicos sintéticos da curcumina: obtenção e avaliação antiparasitária contra Trichomonas vaginalis

Abstract

Trichomonas vaginalis is the etiologic agent of trichomoniasis, a parasitic infection considered to be the most common non-viral sexually transmitted infection by the World Health Organization. Since the 1960s, metronidazole is the standard drug chosen for the treatment of trichomoniasis but many adverse effects, such as allergic reactions, may result from its use. Reports of metronidazole-resistant strains also highlight the importance for the search of new anti-T. vaginalis agents. Considering this, a total of 21 monocarbonyl analogues of curcumin were synthesized and assessed for anti-T. vaginalis activity, as natural curcumin itself has been reported to possess antiparasitic potential. The synthetic products were obtained by aldol condensation of aromatic aldehydes with ketones in yields up to 83%. From the in vitro analysis of the synthetic molecules, untreated trophozoites, and metronidazole, it was observed that two propanone derivatives (3a and 3e), and one derivative of cyclohexanone (5e) exhibited anti-T. vaginalis activity comparable to metronidazole. Optimal antiparasitic concentrations were determined to be 80 μM, 90 μM, and 200 μM for analogues 3a, 3e, and 5e, respectively. Time-kill curves showed that, after 24 hours, the trophozoites were completely inhibited. At the tested concentrations, natural curcumin did not significantly inhibit growth of the trophozoites, therefore demonstrating that the designed synthetic molecules not only have better chemical stability, but also higher anti-T. vaginalis potential. This study suggests that these analogues should be further explored as alternative agents for the treatment of trichomoniasis, and indicates some of the chemical features that apparently enhance antiparasitic activity.