RESUMO
Pentacyclic triterpenes are found in a great variety of natural products and constitute an organic template for the development of new derivative compounds with therapeutic applications. In the present work, lupeol acetate isolated from Chrysophyllum cainito L. fruit was used as a template for the synthesis of novel N-alkyl-arylsulfonamide derivatives, and their synergistic effects with metronidazole against strains of Trichomonas vaginalis were tested. A library of 18 derivatives was synthesized. Ten compounds exhibited an IC50 < 100 µM against a metronidazole-sensitive strain of T. vaginalis. Only seven of these compounds (12, 15, 18-22) also showed activity against metronidazole-resistant strains. The compounds 20 (N-cyclohexyl-p-chlorobenzenesulfonamidolupeol acetate) and 22 (N-cyclohexyl-p-nitrobenzenesulfonamidolupeol acetate) exhibited a similar IC50 against both susceptible and resistant T. vaginalis strains and enhanced the efficacy of metronidazole in a partial and total synergistic way, respectively. These data provided evidence of the trichomonicidal effect of N-alkyl-arylsulfonamide derivatives of lupeol acetate, representing highly promising novel antiparasitic agents.
Assuntos
Trichomonas vaginalis , Metronidazol/farmacologia , Frutas , Triterpenos Pentacíclicos/farmacologia , Acetatos/farmacologiaRESUMO
This review focused on potential regulatory mechanisms of Trichomonas vaginalis virulence properties, cytoadherence, cytotoxicity, phagocytosis, hemolysis, induction of apoptosis, and immune evasion in response to environmental factors of the human urogenital tract, iron, zinc, and polyamines. Understanding the multifactorial nature of trichomonal pathogenesis and its regulation may help to unravel the survival strategies of trichomonads and to implement prevention policies, opportune diagnosis, and alternative treatments for control of trichomoniasis.