Phenotype Screening of an Azole-bisindole Chemical Library Identifies URB1483 as a New Antileishmanial Agent Devoid of Toxicity on Human Cells

Aurora Diotallevi; Laura Scalvini; Gloria Buffi; Yolanda Pérez-Pertejo; Mauro De Santi; Michele Verboni; Gianfranco Favi; Mauro Magnani; Alessio Lodola; Simone Lucarini; Luca Galluzzi

doi:10.1021/acsomega.1c05611

Phenotype Screening of an Azole-bisindole Chemical Library Identifies URB1483 as a New Antileishmanial Agent Devoid of Toxicity on Human Cells

ACS Omega. 2021 Dec 15;6(51):35699-35710. doi: 10.1021/acsomega.1c05611. eCollection 2021 Dec 28.

Affiliations

¹ Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino (PU), Italy.
² Department of Food and Drug, University of Parma, 43124 Parma, Italy.
³ Department of Biomedical Sciences, University of León, 24071 León, Spain.

Abstract

We report the evaluation of a small library of azole-bisindoles for their antileishmanial potential, in terms of efficacy on Leishmania infantum promastigotes and intracellular amastigotes. Nine compounds showed good activity on L. infantum MHOM/TN/80/IPT1 promastigotes with IC₅₀ values ranging from 4 to 10 μM. These active compounds were also tested on human (THP-1, HEPG2, HaCaT, and human primary fibroblasts) and canine (DH82) cell lines. URB1483 was selected as the best compound, with no quantifiable cytotoxicity in mammalian cells, to test the efficacy on intracellular amastigotes. URB1483 significantly reduced the infection index of both human and canine macrophages with an effect comparable to the clinically used drug pentamidine. URB1483 emerges as a new anti-infective agent with remarkable antileishmanial activity and no cytotoxic effects on human and canine cells.