Synthesis and Activity of a New Series of Antileishmanial Agents

Ankush Kanwar; Benjamin J Eduful; Linda Barbeto; Piero Carletti Bonomo; Andrea Lemus; Brian A Vesely; Tina S Mutka; Ala Azhari; Dennis E Kyle; James W Leahy

doi:10.1021/acsmedchemlett.7b00039

Synthesis and Activity of a New Series of Antileishmanial Agents

ACS Med Chem Lett. 2017 Jul 31;8(8):797-801. doi: 10.1021/acsmedchemlett.7b00039. eCollection 2017 Aug 10.

Authors

Affiliations

¹ Department of Chemistry, University of South Florida, CHE 205, 4202 East Fowler Avenue, Tampa, Florida 33620, United States.
² Department of Global Health, College of Public Health, University of South Florida, 3720 Spectrum Boulevard, Suite 304, Tampa, Florida 33612, United States.
³ Florida Center of Excellence for Drug Discovery and Innovation, University of South Florida, 3720 Spectrum Boulevard, Suite 303, Tampa, Florida 33612, United States.
⁴ Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, MDC 7, 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612, United States.

Abstract

We have determined that tetrahydroindazoles such as 1 show potent activity against Leishmania donovani, the causative agent of leishmaniasis. While the Hsp90 activity and anticancer properties of 1 have previously been explored, we present here our efforts to optimize their activity against L. donovani via the synthesis of novel analogues designed to probe the hydrophobic pocket of the protozoan Hsp90 orthologue, specifically through the auspices of functionalization of an amine embedded into the scaffold.

Keywords: Antiinfectives; Hsp90; chaperone; leishmaniasis.