4-(3H)-喹唑啉酮的取代苄基氨基和杂环甲基氨基碳二硫代酸酯衍生物的合成及其细胞毒性活性。

Synthesis of substituted benzylamino- and heterocyclylmethylamino carbodithioate derivatives of 4-(3H)-quinazolinone and their cytotoxic activity.

作者信息

Cao Sheng-Li, Feng Yu-Ping, Zheng Xiao-Lin, Jiang Yu-Yang, Zhang Mei, Wang Yue, Xu Meng

机构信息

Department of Chemistry, Capital Normal University, Beijing, China.

出版信息

Arch Pharm (Weinheim). 2006 May;339(5):250-4. doi: 10.1002/ardp.200500264.

DOI:10.1002/ardp.200500264

PMID:16619282

Abstract

A new series of substituted benzylamino- and heterocyclylmethylamino carbodithioate derivatives of 4-(3H)-quinazolinone were synthesized via four steps starting from 2-amino-5-methylbenzoic acid and initially screened against A-549 (human non-small cell lung cancer), HCT-8 (human colon cancer), and Bel-7402 (human liver cancer) cell lines at the single concentration of 5 microg/mL using the colorimetric MTT assay. The IC50 values were determined for the compounds reaching > or = 70% inhibition in primary screening by serial dilution. Among the newly synthesized compounds, 9n exhibited potent in vitro cytotoxicity against A-549, HCT-8, and Bel-7402 cell lines with the IC50 values of 1.65, 0.93, and 1.43 microM, respectively.

摘要

以2-氨基-5-甲基苯甲酸为起始原料，通过四步反应合成了一系列新的4-(3H)-喹唑啉酮的取代苄氨基和杂环甲基氨基碳二硫代酸酯衍生物，并使用比色MTT法在5μg/mL的单一浓度下对A-549（人非小细胞肺癌）、HCT-8（人结肠癌）和Bel-7402（人肝癌）细胞系进行了初步筛选。通过系列稀释法对在初次筛选中抑制率达到≥70%的化合物测定IC50值。在新合成的化合物中，9n对A-549、HCT-8和Bel-7402细胞系表现出较强的体外细胞毒性，IC50值分别为1.65、0.93和1.43μM。