Master of Science (M.S.)
Degree Granting Department
Roman Manetsch, Ph.D.
Edward Turos, Ph.D.
Wayne Guida, Ph.D.
James Leahy, Ph.D.
Leishmaniasis, Acinetobacter baumannii, antimicrobial, structure-activity relationship
Herein 47 2,4-disubstituted quinazolines were synthesized and tested against Leishmania donovani intracellular amastigotes. A structure-activity relationship was conducted and lead to the identification of quinazolines with EC50s in the single digit and high nanomolar range with favorable antileishmanial selectivity indexes. Quinazoline 2.6 and 2.31 underwent in vivo efficacy studies in murine models of visceral leishmaniasis, reducing liver parasitemia by 12 % and 24 %, respectively, when given by the intraperitoneal route at 15 mg/kg/day x 5 days. The antileishmanial efficacy and easy of synthesis make the 2,4-disubstituted quinazoline compound series a suitable platform for the future development of antileishmanial agents.
A similar series of 50 N2,N4-disubstituted quinazoline-2,4-diamines has also been synthesized and tested against multi-drug resistant strains of Acinetobacter baumannii. Quinazolines with MICs in the single digit micromolar range were identified within the structure-activity relationship. The observed potencies of the top compounds and the easy of synthesis lend to the further investigation of in vivo efficacy studies and could be considered a suitable platform for the future development of anti-bacterial agents against A. baumannii.
Scholar Commons Citation
Barber, Megan Marie, "2,4-Disubstituted Quinazolines with Antileishmanial or Antibacterial Activity" (2015). Graduate Theses and Dissertations.