Design, synthesis and evaluation of thiohydantoin derivatives as potent topoisomerase I (Top1) inhibitors with anticancer activity

被引：66
|
作者：
Majumdar, Papiya [1 ]
Bathula, Chandramohan [2 ]
Basu, Suparna M. [1 ]
Das, Subhendu K. [1 ]
Agarwal, Rahul [3 ]
Hati, Santanu [2 ]
Singh, Ashutosh [3 ]
Sen, Subhabrata [2 ]
Das, Benu Brata [1 ]
机构：
[1] Indian Assoc Cultivat Sci, Dept Phys Chem, Mol Biol Lab, Kolkata 700032, India
[2] Shiv Nadar Univ, Dept Chem, Gautam Buddha Nagar 201314, Uttar Pradesh, India
[3] Shiv Nadar Univ, Dept Life Sci, Gautam Buddha Nagar 201314, Uttar Pradesh, India
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 102卷
基金：
英国惠康基金;
关键词：
Topoisomerase I; Thiohydantoin; Hydantoin; Methylfuro[3,4-c]pyridine-3,4(1H,5H)-dione; Camptothecin; Leishmania bi-subunit topoisomerase I; DNA TOPOISOMERASES; LEISHMANIA; SUBUNIT; CAMPTOTHECIN; HYDANTOIN; TDP1; DISCOVERY; REPAIR;
D O I：
10.1016/j.ejmech.2015.08.032
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
DNA topoisomerase I is a potential chemotherapeutic target. Here, we designed and synthesized a library comprising of hydantoin and thiohydantoin derivatives and tested them against human and Leishmania Top1. One of the thiohydantoin compounds with substituted thiophenyl as the central moiety (compound 15) exhibited potent inhibition of human Top1) through stabilization of Top1-DNA cleavage complexes and showed selective anticancer activity against human cervical carcinoma (HeLa) and breast carcinoma (MCF-7) cell lines. Molecular modeling studies with HTop1 rationalized the inhibitory mechanism of compound 15. (C) 2015 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：540 / 551
页数：12
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