基于2,4-二氨基嘧啶的抗叶酸药物对炭疽芽孢杆菌的合成及生物学评价
Synthesis and biological evaluation of 2,4-diaminopyrimidine-based antifolate drugs against Bacillus anthracis.
作者信息
Nammalwar Baskar, Muddala N Prasad, Bourne Christina R, Henry Mary, Bourne Philip C, Bunce Richard A, Barrow Esther W, Berlin K Darrell, Barrow William W
机构信息
Department of Chemistry, Oklahoma State University, 107 Physical Sciences, Stillwater, OK 74078, USA.
Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078, USA.
出版信息
Molecules. 2014 Mar 17;19(3):3231-46. doi: 10.3390/molecules19033231.
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.
由于细菌天生具有对现有抗生素产生耐药性的能力，因此迫切需要开发新的药物来治疗更具抗药性的菌株。作为我们在该领域研究的延续，我们合成了一系列基于外消旋2,4-二氨基嘧啶的候选药物，并对它们进行了抗炭疽芽孢杆菌的评估。这些结构由一个2,4-二氨基嘧啶环、一个3,4-二甲氧基苄基环和一个N-丙烯酰基取代的1,2-二氢酞嗪环组成。在该结构中，对二氢酞嗪部分的C1立体中心进行了各种改变，并通过测量MIC和K(i)值来评估生物活性，以确定最有效的候选药物。
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