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

• Main Authors: Elena Aguilera, Cintya Perdomo, Alejandra Espindola, Ileana Corvo, Paula Faral-Tello, Carlos Robello, Elva Serna, Fátima Benítez, Rocío Riveros, Susana Torres, Ninfa I. Vera de Bilbao, Gloria Yaluff, Guzmán Alvarez
• Format: Article
• Language: English
• Published: MDPI AG 2019-10-01
• Series: Molecules
• Subjects: anti-<i>t. cruzi</i> activity in vitro and in vivo; anti-<i>leishmania</i> <i>spp</i>. activity in vitro and in vivo; cytotoxicity and genotoxicity
• Online Access: https://www.mdpi.com/1420-3049/24/20/3800

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 <i>Leishmania infantum</i>, <i>Leishmania amazonensis,</i> and <i>Trypanosoma cruzi</i> 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 <b>8</b> (ID_<b>1260)</b> was active in vitro (IC₅₀ 200 nM) and in vivo (60% infection reduction at 50 mg/kg) in <i>Leishmania</i> and <i>T. cruzi</i>. It also has low toxicity in vitro and in vivo (LD₅₀ &gt;2000 mg/kg) and no genotoxic effects, being a promising compound for anti-trypanosomatid drug development.