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Eur J Med Chem ; 143: 632-645, 2018 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-29216562

RESUMEN

Sexually transmitted diseases like trichomoniasis along with opportunistic fungal infections like candidiasis are major global health burden in female reproductive health. In this context a novel non-nitroimidazole class of substituted carbamothioic amine-1-carbothioic thioanhydride series was designed, synthesized, evaluated for trichomonacidal and fungicidal activities, and was found to be more active than the standard drug Metronidazole (MTZ). Compounds were trichomonicidal in the MIC ranges of 4.77-294.1 µM and 32.46-735.20 µM against MTZ-susceptible and -resistant strains, respectively. Further, compounds inhibited the growth of at least two out of ten fungal strains tested at MIC of 7.50-240.38 µM. The most active compound (20) of this series was 3.8 and 9.5 fold more active than the MTZ against the two Trichomonas strains tested. Compound 20 also significantly inhibited the sulfhydryl groups present over Trichomonas vaginalis and was found to be more active than the MTZ in vivo. Further, a docking analysis carried out with cysteine proteases supported their thiol inhibiting ability and preliminary pharmacokinetic study has shown good distribution and systemic clearance.


Asunto(s)
Anhidrasas Carbónicas/farmacología , Diseño de Fármacos , Fungicidas Industriales/farmacología , Compuestos de Sulfhidrilo/farmacología , Trichomonas/efectos de los fármacos , Anhidrasas Carbónicas/síntesis química , Anhidrasas Carbónicas/química , Relación Dosis-Respuesta a Droga , Fungicidas Industriales/síntesis química , Fungicidas Industriales/química , Metronidazol/química , Metronidazol/farmacología , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Relación Estructura-Actividad , Compuestos de Sulfhidrilo/síntesis química , Compuestos de Sulfhidrilo/química , Trichomonas/crecimiento & desarrollo
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