A Nature-Inspired Design Yields a New Class of Steroids Against Trypanosomatids

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2019 Oct 27

PMID 31652542

Citations 8

Authors

Elena Aguilera

Cintya Perdomo

Alejandra Espindola

Ileana Corvo

Paula Faral-Tello

Carlos Robello

Elva Serna

Fatima Benitez

Rocio Riveros

Susana Torres

Ninfa I Vera de Bilbao

Gloria Yaluff

Guzman Alvarez

Affiliations

Soon will be listed here.

Abstract

Chagas disease and Leishmaniasis are neglected endemic protozoan diseases recognized as public health problems by the World Health Organization. These diseases affect millions of people around the world however, efficient and low-cost treatments are not available. Different steroid molecules with antimicrobial and antiparasitic activity were isolated from diverse organisms (ticks, plants, fungi). These molecules have complex structures that make de novo synthesis extremely difficult. In this work, we designed new and simpler compounds with antiparasitic potential inspired in natural steroids and synthesized a series of nineteen steroidal arylideneketones and thiazolidenehydrazines. We explored their biological activity against , and in vitro and in vivo. We also assayed their genotoxicity and acute toxicity in vitro and in mice. The best compound, a steroidal thiosemicarbazone compound (ID_ was active in vitro (IC 200 nM) and in vivo (60% infection reduction at 50 mg/kg) in and . It also has low toxicity in vitro and in vivo (LD >2000 mg/kg) and no genotoxic effects, being a promising compound for anti-trypanosomatid drug development.

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