Identification of a Hit Series of Antileishmanial Compounds through the Use of Mixture-Based Libraries

Marc A Giulianotti; Brian A Vesely; Ala Azhari; Ashley Souza; Travis LaVoi; Richard A Houghten; Dennis E Kyle; James W Leahy

doi:10.1021/acsmedchemlett.7b00045

Identification of a Hit Series of Antileishmanial Compounds through the Use of Mixture-Based Libraries

ACS Med Chem Lett. 2017 Jul 10;8(8):802-807. doi: 10.1021/acsmedchemlett.7b00045. eCollection 2017 Aug 10.

Authors

Marc A Giulianotti^{1

2}, Brian A Vesely³, Ala Azhari³, Ashley Souza³, Travis LaVoi², Richard A Houghten², Dennis E Kyle³, James W Leahy^{1

4

5}

Affiliations

¹ Department of Chemistry, University of South Florida, CHE 205, 4202 East Fowler Avenue, Tampa, Florida 33620, United States.
² Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, Florida 34987, United States.
³ Department of Global Health, College of Public Health, University of South Florida, 3720 Spectrum Boulevard, Suite 304, Tampa, Florida 33612, United States.
⁴ Florida Center of Excellence for Drug Discovery and Innovation, University of South Florida, 3720 Spectrum Boulevard, Suite 303, Tampa, Florida 33612, United States.
⁵ 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

From a screening campaign that included mixture-based libraries containing more than 6 million compounds, a lead series of bis-cyclic guanidines was identified as the most promising. Lead optimization resulted in the identification of potent (IC₅₀ < 500 nM) and selective compounds within this series as well as potent and selective monoguanidines.

Keywords: Leishmaniasis; lead optimization; mixture-based libraries; screening.