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

Molecules

Baskar Nammalwar¹  N. Prasad Muddala¹  Christina R. Bourne²  Mary Henry²  Philip C. Bourne²  Richard A. Bunce¹  Esther W. Barrow²  K. Darrell Berlin¹ 

[1] Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA; E-Mails:;Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA; E-Mails:

关键词: Gram-positive bacteria;    Bacillus anthracis;    2;    4-diaminopyrimidine;    Heck reaction;    antibiotic resistance;    dihydrofolate reductase (DHFR);    antifolates;   

DOI  :  10.3390/molecules19033231

来源: mdpi

【 摘 要 】

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 K_i values to identify the most potent drug candidate.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.