Danac Ramona, Mangalagiu Ionel I
"Al. I. Cuza" University of Iasi, Organic and Biochemistry Department, Bd. Carol 11, 700506 Iasi, Romania.
"Al. I. Cuza" University of Iasi, Organic and Biochemistry Department, Bd. Carol 11, 700506 Iasi, Romania.
Eur J Med Chem. 2014 Mar 3;74:664-70. doi: 10.1016/j.ejmech.2013.09.061. Epub 2013 Nov 7.
Three classes of fused bipyridine heterocycles were designed, synthesized and evaluated for their antimycobacterial activities. The method for preparation of fused bipyridine derivatives is straight and efficient. The primary antimycobacterial screening reveals that mono-indolizine mono-salts are displaying potency superior to the second-line antitubercular drugs Cycloserine and Pyrimethamine and, equal as the first line anti-TB Ethambutol. The data from Cycle-2 screening assay (MIC, MBC, LORA, intracellular (macrophage) drug screening, and MTT cell proliferation) confirm the promising anti-TB results from Cycle-1 for mono-indolizine mono-salts. These data indicate that mono-indolizine mono-salt 6d is a potent compound against both replicating and non-replicating Mycobacterium tuberculosis, is active against both extracellular and intracellular organisms, has a bacteriostatic mechanism of action and has basically no toxicity. We see no influence concerning the anti-TB activity of the fused-pyridine substituents.
设计、合成了三类稠合联吡啶杂环化合物，并对其抗分枝杆菌活性进行了评估。稠合联吡啶衍生物的制备方法直接且高效。初步抗分枝杆菌筛选显示，单吲哚嗪单盐的效力优于二线抗结核药物环丝氨酸和乙胺嘧啶，与一线抗结核药物乙胺丁醇相当。来自第二轮筛选试验（MIC、MBC、LORA、细胞内（巨噬细胞）药物筛选和MTT细胞增殖）的数据证实了第一轮中关于单吲哚嗪单盐的抗结核结果很有前景。这些数据表明，单吲哚嗪单盐6d是一种对复制型和非复制型结核分枝杆菌均有效的化合物，对细胞外和细胞内生物体均有活性，具有抑菌作用机制且基本无毒性。我们未发现稠合吡啶取代基对抗结核活性有影响。
