Synthesis and antiproliferative activity of 3-aryl-2-(1H-benzotriazol-1-yl)acrylonitriles.: Part III
Synthesis and antiproliferative activity of 3-aryl-2-(1H-benzotriazol-1-yl)acrylonitriles.: Part III
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DOI：
10.1016/s0223-5234(02)01411-3
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发表时间：
2002-11-01
影响因子：
6.7
通讯作者：
Loddo, R
中科院分区：
文献类型：
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作者：
Carta, A;Sanna, P;Loddo, R
合成了30个新系列的3-芳基-2-（1h -苯并三唑-1-基）丙烯腈，并进行了生物活性测试，作为抗菌和抗肿瘤研究的一部分。特别地，题目化合物在体外对革兰氏阳性和革兰氏阴性细菌（金黄色葡萄球菌、沙门氏菌）、分枝杆菌（福氏分枝杆菌、耻垢分枝杆菌ATCC 19420和结核分枝杆菌ATCC 27294）、酵母和霉菌（白色念珠菌ATCC 10231和烟曲霉）的代表性菌株进行了评价。此外，在MT-4细胞中测定了它们对HIV-1的抗逆转录病毒活性和细胞毒性。在这些分析中，标题化合物和47个先前描述的附加衍生物(P. Sanna， A. Carta， M.E. Rahbar Nikookar, Eur。医学化学杂志35 (2000)535-543；P. Sanna， A. Carta， L. Gherardini， M.E. Rahbar Nikookar, Farmaco 57(2002) 79-87)对其阻止MT-4细胞生长的能力进行了测试。所有化合物均缺乏抗菌、抗真菌和抗hiv -1活性。在抗分枝杆菌试验中，几种化合物对结核分枝杆菌有活性（MIC50 = 6.0-70 muM）。然而，由于它们在较低浓度（CC50 = 0.05-25 muM）下对MT-4细胞显示细胞毒性，因此它们的抗分枝杆菌活性不是选择性的。由于这个原因，大多数细胞毒性化合物也被评估了对来自血液学和实体瘤的人类细胞系的抗增殖活性。化合物34对上述人类肿瘤源性细胞系的抑制作用最强。(C) 2002年由Elsevier SAS出版的Editions scientifiques et medicales。
A new series of 30 3-aryl-2-(1H-benzotriazol-1-yl)acrylonitriles were synthesized and tested for biological activity as part of our research in the antimicrobial and antitumor fields. In particular, title compounds were evaluated in vitro against representative strains of Gram-positive and Gram-negative bacteria (S. aureus, Salmonella spp), mycobacteria (M. fortuitum, M. smegmatis ATCC 19420 and M. tuberculosis ATCC 27294), yeast and mould (C. albicans ATCC 10231 and A. fumigatus). Furthermore, their antiretroviral activity against HIV-1 was determined in MT-4 cells together with cytotoxicity. In these assays title compounds and 47 additional derivatives described previously (P. Sanna, A. Carta, M.E. Rahbar Nikookar, Eur. J. Med. Chem. 35 (2000) 535-543; P. Sanna, A. Carta, L. Gherardini, M.E. Rahbar Nikookar, Farmaco 57 (2002) 79-87) were tested for their capability to prevent MT-4 cell growth. All compounds resulted devoid of antibacterial, antifungal and anti-HIV-1 activity. In anti-mycobacterial assays several compounds resulted active (MIC50 = 6.0-70 muM) against M. tuberculosis. However, since they showed cytotoxicity against MT-4 cells at lower concentrations (CC50 = 0.05-25 muM), their anti-mycobacterial activity was not selective. For this reason, the most cytotoxic compounds were also evaluated for antiproliferative activity against a panel of human cell lines derived from both hematological and solid tumors. Compound 34 resulted the most potent compound against the above human tumor-derived cell lines. (C) 2002 Published by Editions scientifiques et medicales Elsevier SAS.