Onnis Valentina, De Logu Alessandro, Cocco Maria T, Fadda Roberta, Meleddu Rita, Congiu Cenzo
Dipartimento di Tossicologia, Sezione di Chimica Farmaceutica, Università degli Studi di Cagliari, via Ospedale 72, Cagliari I-09124, Italy.
Eur J Med Chem. 2009 Mar;44(3):1288-95. doi: 10.1016/j.ejmech.2008.08.003. Epub 2008 Aug 22.
The synthesis and antifungal activity of 2-acylhydrazino-5-arylpyrroles 21-62 are described. Pyrrole derivatives 21-62 were evaluated for their antifungal activity towards Candida albicans ATCC 10231 and three Candida non-albicans isolated from clinical specimens. Most of them showed very good antifungal activities against Candidae, having MIC values in the 0.39-3.12 microg/mL range and enhanced inhibition potency as compared to that of fluconazole. In addition, some of the most active compounds were tested for cytotoxic activities against breast (MCF-7), lung (H-460), and central nervous system (SF-268) human cancer cell lines with the NCI anticancer drug screen. The activity of pyrroles described in this paper, along with the low toxicity, shows promise for the future development of non-toxic new antimycotic agents. The relationship between functional group variation and biological activity of the evaluated compounds is also discussed.
描述了2-酰肼基-5-芳基吡咯21-62的合成及其抗真菌活性。对吡咯衍生物21-62针对白色念珠菌ATCC 10231以及从临床标本中分离出的三种非白色念珠菌的抗真菌活性进行了评估。它们中的大多数对念珠菌显示出非常好的抗真菌活性，MIC值在0.39-3.12微克/毫升范围内，并且与氟康唑相比具有增强的抑制效力。此外，使用美国国立癌症研究所抗癌药物筛选方法，对一些活性最强的化合物针对乳腺（MCF-7）、肺（H-460）和中枢神经系统（SF-268）人类癌细胞系进行了细胞毒性活性测试。本文所述吡咯的活性以及低毒性表明其有望用于无毒新型抗真菌剂的未来开发。还讨论了所评估化合物的官能团变化与生物活性之间的关系。
