Hassanzadeh Farshid, Sadeghi-Aliabadi Hojjat, Jafari Elham, Sharifzadeh Azadeh, Dana Nasim
Department of Medicinal Chemistry, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Res Pharm Sci. 2019 Oct 4;14(5):408-413. doi: 10.4103/1735-5362.268201. eCollection 2019 Oct.
1, 3, 4- Oxadiazoles and quinazolinones are privileged structures with extensive biological activities. On account of reported anticancer activity of them, in this study, a multi-step reaction procedure has been developed for the synthesis of some quinazolinone-1, 3, 4-oxadiazole derivatives. Reaction of the synthesized 3-amino-4(3H) quinazolinone derivatives with chloroacetyl chloride in the presence of dichloromethane/triethylamine yielded 2-chloro -N-(4-oxo-2-quinazolin3 (3H)-yl) acetamide derivatives as intermediate. Treatment of the resultants with 5- (4-chlorophenyl) 1, 3, 4-oxadiazole-2-thiol in dry acetone and potassium carbonate gave coupled derivatives of quinazolinone-1, 3, 4-oxadiazole. The cytotoxic effect of final compounds was tested against MCF-7 and HeLa cell lines using MTT assay. Compound 2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio) N-(4-oxo-2-propylquinazolin)3(4H)acatamide 6a exhibited remarkable cytotoxic activity at 10 and 100 μM against HeLa cell line. The alteration of substituents on C2 of quinazolinone ring revealed that the introduction of propyl moeity improved cytotoxic activity against HeLa cell line.
1,3,4-恶二唑和喹唑啉酮是具有广泛生物活性的优势结构。鉴于它们已报道的抗癌活性，在本研究中，已开发出一种多步反应程序来合成一些喹唑啉酮-1,3,4-恶二唑衍生物。合成的3-氨基-4(3H)喹唑啉酮衍生物在二氯甲烷/三乙胺存在下与氯乙酰氯反应，生成2-氯-N-(4-氧代-2-喹唑啉-3(3H)-基)乙酰胺衍生物作为中间体。将所得产物与5-(4-氯苯基)-1,3,4-恶二唑-2-硫醇在干燥丙酮和碳酸钾中处理，得到喹唑啉酮-1,3,4-恶二唑的偶联衍生物。使用MTT法测试了最终化合物对MCF-7和HeLa细胞系的细胞毒性作用。化合物2-(5-(4-氯苯基)-1,3,4-恶二唑-2-基硫代)-N-(4-氧代-2-丙基喹唑啉)3(4H)酰胺6a在10和100μM浓度下对HeLa细胞系表现出显著的细胞毒性活性。喹唑啉酮环C2上取代基的改变表明，丙基部分的引入提高了对HeLa细胞系的细胞毒性活性。
