title: Synthesis and biological evaluation of 2,4-diaminopyrimidine-based antifolate drugs against Bacillus anthracis.
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 K(i) values to identify the most potent drug candidate.
authors.affiliation: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA. baskar@okstate.edu.
authors.forename: Baskar
authors.initials: B
authors.lastname: Nammalwar
authors.affiliation: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA. muddala@okstate.edu.
authors.forename: N Prasad
authors.initials: NP
authors.lastname: Muddala
authors.affiliation: Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA. cbourne@ou.edu.
authors.forename: Christina R
authors.initials: CR
authors.lastname: Bourne
authors.affiliation: Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA. henrym@okstate.edu.
authors.forename: Mary
authors.initials: M
authors.lastname: Henry
authors.affiliation: Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA. pcbourne@yahoo.com.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Bourne
authors.affiliation: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA. rab@okstate.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bunce
authors.affiliation: Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA. esther.barrow@okstate.edu.
authors.forename: Esther W
authors.initials: EW
authors.lastname: Barrow
authors.affiliation: Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA. kdb@okstate.edu.
authors.forename: K Darrell
authors.initials: KD
authors.lastname: Berlin
authors.affiliation: Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA. bill.barrow@okstate.edu.
authors.forename: William W
authors.initials: WW
authors.lastname: Barrow
mesh_terms: D001408:Bacillus anthracis / Q000187:drug effects*; D001665:Binding Sites; D005493:Folic Acid Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry
chemical_list: D005493:Folic Acid Antagonists; D011743:Pyrimidines; C017205:2,4-diaminopyrimidine; D013762:Tetrahydrofolate Dehydrogenase