Synthesis and Biological Evaluation of 2,4-Diaminopyrimidine-Based Antifolate Drugs against Bacillus anthracis
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,...
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doaj-9d94526dc14345a597e35fe0c54840902020-11-24T20:57:07ZengMDPI AGMolecules1420-30492014-03-011933231324610.3390/molecules19033231molecules19033231Synthesis and Biological Evaluation of 2,4-Diaminopyrimidine-Based Antifolate Drugs against Bacillus anthracisBaskar Nammalwar0N. Prasad Muddala1Christina R. Bourne2Mary Henry3Philip C. Bourne4Richard A. Bunce5Esther W. Barrow6K. Darrell Berlin7William W. Barrow8Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USADepartment of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USADepartment of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USADepartment of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USADepartment of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USADepartment of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USADepartment of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USADepartment of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USADepartment of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USADue 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.http://www.mdpi.com/1420-3049/19/3/3231Gram-positive bacteriaBacillus anthracis2,4-diaminopyrimidineHeck reactionantibiotic resistancedihydrofolate reductase (DHFR)antifolates |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Synthesis and Biological Evaluation of 2,4-Diaminopyrimidine-Based Antifolate Drugs against Bacillus anthracis Molecules Gram-positive bacteria Bacillus anthracis 2,4-diaminopyrimidine Heck reaction antibiotic resistance dihydrofolate reductase (DHFR) antifolates |
author_facet |
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 |
author_sort |
Baskar Nammalwar |
title |
Synthesis and Biological Evaluation of 2,4-Diaminopyrimidine-Based Antifolate Drugs against Bacillus anthracis |
title_short |
Synthesis and Biological Evaluation of 2,4-Diaminopyrimidine-Based Antifolate Drugs against Bacillus anthracis |
title_full |
Synthesis and Biological Evaluation of 2,4-Diaminopyrimidine-Based Antifolate Drugs against Bacillus anthracis |
title_fullStr |
Synthesis and Biological Evaluation of 2,4-Diaminopyrimidine-Based Antifolate Drugs against Bacillus anthracis |
title_full_unstemmed |
Synthesis and Biological Evaluation of 2,4-Diaminopyrimidine-Based Antifolate Drugs against Bacillus anthracis |
title_sort |
synthesis and biological evaluation of 2,4-diaminopyrimidine-based antifolate drugs against bacillus anthracis |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2014-03-01 |
description |
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. |
topic |
Gram-positive bacteria Bacillus anthracis 2,4-diaminopyrimidine Heck reaction antibiotic resistance dihydrofolate reductase (DHFR) antifolates |
url |
http://www.mdpi.com/1420-3049/19/3/3231 |
work_keys_str_mv |
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