Synthesis and Biological Evaluation of 2,4-Diaminopyrimidine-Based Antifolate Drugs against Bacillus anthracis

Baskar Nammalwar; N. Prasad Muddala; Christina R. Bourne; Mary Henry; Philip C. Bourne; Richard A. Bunce; Esther W. Barrow; K. Darrell Berlin; William W. Barrow

doi:10.3390/molecules19033231

Molecules (Mar 2014)

Synthesis and Biological Evaluation of 2,4-Diaminopyrimidine-Based Antifolate Drugs against Bacillus anthracis

Baskar Nammalwar,
N. Prasad Muddala,
Christina R. Bourne,
Mary Henry,
Philip C. Bourne,
Richard A. Bunce,
Esther W. Barrow,
K. Darrell Berlin,
William W. Barrow

Affiliations

Baskar Nammalwar: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA
N. Prasad Muddala: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA
Christina R. Bourne: Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA
Mary Henry: Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA
Philip C. Bourne: Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA
Richard A. Bunce: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA
Esther W. Barrow: Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA
K. Darrell Berlin: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA
William W. Barrow: Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA

DOI: https://doi.org/10.3390/molecules19033231
Journal volume & issue: Vol. 19, no. 3
pp. 3231 – 3246

Abstract

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Due to the innate ability of bacteria to develop resistance to available antibiotics, there is a critical need to develop new agents to treat more resilient strains. As a continuation of our research in this area, we have synthesized a series of racemic 2,4-diaminopyrimidine-based drug candidates, and evaluated them against Bacillus anthracis. The structures are comprised of a 2,4-diaminopyrimidine ring, a 3,4-dimethoxybenzyl ring, and an N-acryloyl-substituted 1,2-dihydrophthalazine ring. Various changes were made at the C1 stereocenter of the dihydrophthalazine moiety in the structure, and the biological activity was assessed by measurement of the MIC and Ki values to identify the most potent drug candidate.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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