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三唑并喹唑啉酮杂化物某些衍生物的合成与细胞毒性评价

Synthesis and cytotoxic evaluation of some derivatives of triazole-quinazolinone hybrids.

作者信息

Hassanzadeh Farshid, Sadeghi-Aliabadi Hojjat, Nikooei Shadan, Jafari Elham, Vaseghi Golnaz

机构信息

Department of Medicinal Chemistry and 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.

出版信息

Res Pharm Sci. 2019 Mar 8;14(2):130-137. doi: 10.4103/1735-5362.253360. eCollection 2019 Apr.

Abstract

Triazoles and quinazolinones are important heterocyclic structures with diverse biological properties including cytotoxic, antibacterial, antifungal and anticonvulsant activities. Due to valuable cytotoxic effects of both triazole and quinazoline derivatives, in this study a series of quinazolinone-triazole hybrids were synthesized in a multiple-step reaction procedure. 3-Amino-quinazolinone derivatives were treated with chloroacetyl chloride in the presence of dichloromethane/triethylamine to afford 2-chloro -N-(4-oxo-2- quinazolin3 (3H)-yl) acetamide derivatives. The reaction of resultants with 4-mehyl-4-H-1, 2, 4-triazole-3- thiol in dry acetone and potassium carbonate led to the formation of final products. Synthesized compounds were evaluated for their cytotoxic effects against MCF-7 and Hela cell lines using MTT colorimetric assay. Amongst tested compounds, showed the highest cytotoxic activity against MCF7 cell line at all tested concentrations while compounds and indicated mild cytotoxic effects against Hela cell line at highest tested concentration reducing cell viability about 40%. The IC50 values of tested compounds revealed that the MCF-7 is more susceptible to the compound .

摘要

三唑和喹唑啉酮是重要的杂环结构,具有多种生物学特性,包括细胞毒性、抗菌、抗真菌和抗惊厥活性。由于三唑和喹唑啉衍生物都具有宝贵的细胞毒性作用,在本研究中,通过多步反应程序合成了一系列喹唑啉酮 - 三唑杂化物。在二氯甲烷/三乙胺存在下,用氯乙酰氯处理3 - 氨基喹唑啉酮衍生物,得到2 - 氯 - N -(4 - 氧代 - 2 - 喹唑啉 - 3(3H) - 基)乙酰胺衍生物。所得产物与4 - 甲基 - 4 - H - 1,2,4 - 三唑 - 3 - 硫醇在干燥丙酮和碳酸钾中反应,生成最终产物。使用MTT比色法评估合成化合物对MCF - 7和Hela细胞系的细胞毒性作用。在测试的化合物中, 在所有测试浓度下对MCF7细胞系表现出最高的细胞毒性活性,而化合物 和 在最高测试浓度下对Hela细胞系表现出轻微的细胞毒性作用,使细胞活力降低约40%。测试化合物的IC50值表明,MCF - 7对化合物 更敏感。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a89b/6791177/14b0cfce31ab/RPS-14-130-g001.jpg

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