Department of Biochemical and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes, 580, Bloco 16, Butantã, São Paulo, SP 05508-900, Brazil.
Bioorg Med Chem. 2011 Nov 1;19(21):6292-301. doi: 10.1016/j.bmc.2011.09.009. Epub 2011 Sep 10.
A series of 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazole derivatives was synthesized and their activity screened in vitro against Staphylococcus aureus, Trypanosoma cruzi, and Candida albicans. The bioactivity was expressed as minimum inhibitory concentration (MIC) for S. aureus strains, and as fifty-percent inhibitory concentration (IC(50)) of parasite population growth for T. cruzi. A molecular modeling approach was performed to establish qualitative relationships regarding the biological data and the compounds' physicochemical properties. The 5-(4-OC(4)H(9)Ph, 5l), and 5-(4-CO(2)CH(3)Ph, 5o) derivatives were the most active compounds for S. aureus ATCC 25923 (MIC=1.95-1.25 μg/mL) and T. cruzi (IC(50)=7.91 μM), respectively. Also, a preliminary evaluation against C. albicans involving some compounds was performed and the 5-(4-CH(3)Ph, 5e) derivative was the most active compound (MIC=3.28-2.95 μg/mL). In this preliminary study, all synthesized 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazole derivatives were active against all microorganisms tested.
一系列 3-乙酰基-2,5-二取代-2,3-二氢-1,3,4-噁二唑衍生物被合成，并在体外对金黄色葡萄球菌、克氏锥虫和白色念珠菌进行了活性筛选。生物活性用最小抑菌浓度（MIC）表示，用于金黄色葡萄球菌菌株，用寄生虫群体生长的 50%抑制浓度（IC(50)）表示，用于克氏锥虫。进行了一种分子建模方法，以建立关于生物数据和化合物物理化学性质的定性关系。5-(4-OC(4)H(9)Ph, 5l)和 5-(4-CO(2)CH(3)Ph, 5o)衍生物对金黄色葡萄球菌 ATCC 25923（MIC=1.95-1.25 μg/mL）和克氏锥虫（IC(50)=7.91 μM）最为活跃。此外，还对一些化合物进行了针对白色念珠菌的初步评估，其中 5-(4-CH(3)Ph, 5e)衍生物的活性最高（MIC=3.28-2.95 μg/mL）。在这项初步研究中，所有合成的 3-乙酰基-2,5-二取代-2,3-二氢-1,3,4-噁二唑衍生物对所有测试的微生物都具有活性。
