2. Academic Validation
  3. Antileishmanial activity of a series of N²,N⁴-disubstituted quinazoline-2,4-diamines

Antileishmanial activity of a series of N²,N⁴-disubstituted quinazoline-2,4-diamines

  • J Med Chem. 2014 Jun 26;57(12):5141-56. doi: 10.1021/jm5000408.
Kurt S Van Horn 1,  Xiaohua Zhu,  Trupti Pandharkar,  Sihyung Yang,  Brian Vesely,  Manu Vanaerschot,  Jean-Claude Dujardin,  Suman Rijal,  Dennis E Kyle,  Michael Zhuo Wang,  Karl A Werbovetz,  Roman Manetsch
Affiliations

Affiliation

  • 1 Department of Chemistry, University of South Florida , 4202 East Fowler Avenue, CHE 205, Tampa, Florida 33620, United States.
PMID: 24874647 DOI: 10.1021/jm5000408
Abstract

A series of N(2),N(4)-disubstituted quinazoline-2,4-diamines has been synthesized and tested against Leishmania donovani and L. amazonensis intracellular amastigotes. A structure-activity and structure-property relationship study was conducted in part using the Topliss operational scheme to identify new lead compounds. This study led to the identification of quinazolines with EC50 values in the single digit micromolar or high nanomolar range in addition to favorable physicochemical properties. Quinazoline 23 also displayed efficacy in a murine model of visceral leishmaniasis, reducing liver parasitemia by 37% when given by the intraperitoneal route at 15 mg kg(-1) day(-1) for 5 consecutive days. Their antileishmanial efficacy, ease of synthesis, and favorable physicochemical properties make the N(2),N(4)-disubstituted quinazoline-2,4-diamine compound series a suitable platform for future development of antileishmanial agents.

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