Discovery of New Chemical Tools against Leishmania amazonensis via the MMV Pathogen Box

Pharmaceuticals

Atteneri López-Arencibia¹  Ines Sifaoui¹  Desirée San Nicolás-Hernández¹  José E. Piñero¹  María Reyes-Batlle¹  Jacob Lorenzo-Morales¹  Carlos J. Bethencourt-Estrella¹ 

[1] Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Campus de Anchieta, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203 La Laguna, Spain;

关键词: Leishmania amazonensis;    screening;    chemotherapy;    Pathogen Box;    hits;   

DOI  :  10.3390/ph14121219

来源: DOAJ

【 摘 要 】

The protozoan parasite Leishmania causes a spectrum of diseases and there are over 1 million infections each year. Current treatments are toxic, expensive, and difficult to administer, and resistance to them is emerging. In this study, we screened the antileishmanial activity of the Pathogen Box compounds from the Medicine for Malaria Venture against Leishmania amazonensis, and compared their structures and cytotoxicity. The compounds MMV676388 (3), MMV690103 (5), MMV022029 (7), MMV022478 (9) and MMV021013 (10) exerted a significant dose-dependent inhibition effect on the proliferation of L. amazonensis promastigotes and intracellular amastigotes. Moreover, studies on the mechanism of cell death showed that compounds 3 and 5 induced an apoptotic process while the compounds 7, 9 and 10 seem to induce an autophagic mechanism. The present findings underline the potential of these five molecules as novel therapeutic leishmanicidal agents.

【 授权许可】

Unknown