Investigation of C-5 alkynyl (alkynyloxy or hydroxymethyl) and/or N-3 propynyl substituted pyrimidine nucleoside analogs as a new class of antimicrobial agents
作者:Saurabh Garg、Neeraj Shakya、Naveen C. Srivastav、Babita Agrawal、Dennis Y. Kunimoto、Rakesh Kumar
DOI:10.1016/j.bmc.2016.09.008
日期:2016.11
infections and the emergence of drug-resistant strains urgently require a new class of agents that are distinct than current therapies. A group of 5-ethynyl (6–10), 5-(2-propynyloxy) (16, 18, 20, 22, 24), 5-(2-propynyloxy)-3-N-(2-propynyl) (17, 19, 21, 23, 25) and 5-hydroxymethyl-3-N-(2-propynyl) (30–33) derivatives of pyrimidine nucleosides were synthesized and evaluated against mycobacteria [Mycobacterium
分支杆菌感染的复发和耐药菌株的出现迫切需要一类不同于当前疗法的新型药物。A组5-乙炔基(的6 - 10),5-(2-丙炔氧基)(16,18,20,22,24),5-(2-丙炔氧基)-3- ñ - (2-丙炔基)(17,19,21,23,25)和5-羟甲基-3- ñ - (2-丙炔基)(30 - 33)的嘧啶核苷衍生物的合成和对分枝杆菌[评价结核分枝杆菌(Mtb),牛分枝杆菌(BCG)和鸟分枝杆菌),革兰氏阳性菌(金黄色葡萄球菌和粪肠球菌)和革兰氏阴性菌(大肠杆菌,鼠伤寒沙门氏菌和铜绿假单胞菌与单独的药物合用)体外测定。尽管几种化合物在较高浓度下对Mtb,牛分枝杆菌,金黄色葡萄球菌和粪肠球菌均表现出明显的抑制活性。,它们在较低的浓度下与抗结核药异烟肼和利福平以及抗菌药庆大霉素具有出乎意料的协同作用和加性相互作用。还发现了活性类似物在感染了H37Ra的人单核细胞系中抑制细胞内Mtb。5-羟甲基-3-口服给药ñ