Molecules 2014, 19(3), 3231-3246; doi:10.3390/molecules19033231
Article

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

Received: 11 January 2014; in revised form: 8 March 2014 / Accepted: 10 March 2014 / Published: 17 March 2014
(This article belongs to the Special Issue Heterocyclic and Medicinal Chemistry)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: 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.
Keywords: Gram-positive bacteria; Bacillus anthracis; 2,4-diaminopyrimidine; Heck reaction; antibiotic resistance; dihydrofolate reductase (DHFR); antifolates
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MDPI and ACS Style

Nammalwar, B.; Muddala, N.P.; Bourne, C.R.; Henry, M.; Bourne, P.C.; Bunce, R.A.; Barrow, E.W.; Berlin, K.D.; Barrow, W.W. Synthesis and Biological Evaluation of 2,4-Diaminopyrimidine-Based Antifolate Drugs against Bacillus anthracis. Molecules 2014, 19, 3231-3246.

AMA Style

Nammalwar B, Muddala NP, Bourne CR, Henry M, Bourne PC, Bunce RA, Barrow EW, Berlin KD, Barrow WW. Synthesis and Biological Evaluation of 2,4-Diaminopyrimidine-Based Antifolate Drugs against Bacillus anthracis. Molecules. 2014; 19(3):3231-3246.

Chicago/Turabian Style

Nammalwar, Baskar; Muddala, N. P.; Bourne, Christina R.; Henry, Mary; Bourne, Philip C.; Bunce, Richard A.; Barrow, Esther W.; Berlin, K. D.; Barrow, William W. 2014. "Synthesis and Biological Evaluation of 2,4-Diaminopyrimidine-Based Antifolate Drugs against Bacillus anthracis." Molecules 19, no. 3: 3231-3246.

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