Synthesis of DNA interactive C3-trans-cinnamide linked β-carboline conjugates as potential cytotoxic and DNA topoisomerase I inhibitors

被引:26
作者
Sathish, Manda [1 ]
Dushantrao, Sabanis Chetan [2 ]
Nekkanti, Shalini [2 ]
Tokala, Ramya [2 ]
Thatikonda, Soujanya [3 ]
Tangella, Yellaiah [1 ]
Srinivas, Gunda [4 ]
Cherukommu, Shirisha [4 ]
Krishna, Namballa Hari [2 ]
Shankaraiah, Nagula [2 ]
Nagesh, Narayana [4 ]
Kamal, Ahmed [1 ,5 ]
机构
[1] CSIR Indian Inst Chem Technol, Med Chem & Biotechnol, Hyderabad 500007, Telangana, India
[2] NIPER, Dept Med Chem, Hyderabad 500037, Telangana, India
[3] NIPER, Dept Regulatory Toxicol, Hyderabad 500037, Telangana, India
[4] CSIR Ctr Cellular & Mol Biol, Hyderabad 500007, Telangana, India
[5] Jamia Hamdard, SPER, New Delhi 110062, India
关键词
beta-Carbolines; Trans-cinnamides; DNA intercalation; Topoisomerase I; Anticancer activity; CINNAMIC ACID-DERIVATIVES; P-ARYLTHIO CINNAMIDES; ANTICANCER ACTIVITY; CC-1065; NSC-298223; BINDING PROPERTIES; APOPTOSIS; CANCER; DESIGN; COMPLEXES; ABILITY;
D O I
10.1016/j.bmc.2018.08.031
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A series of new C3-trans-cinnamide linked beta-carboline conjugates has been synthesized by coupling between various beta-carboline amines and substituted cinnamic acids. Evaluation of their anti-proliferative activity against a panel of selected human cancer cell lines such as A549 (lung cancer), MCF-7 (breast cancer), B16 (melanoma), HeLa (cervical cancer) and a normal cell line NIH3T3 (mouse embryonic fibroblast cell line), suggested that the newly designed conjugates are considerably active against all the tested cancer cell lines with IC50 values 13-45 nM. Moreover, the conjugates 8v and 8x were the most active against MCF-7 cells (14.05 nM and 13.84 nM respectively) and also even potent on other cell lines tested. Further, detailed investigations such as cell cycle analysis, apoptosis induction study, topoisomerase I inhibition assay, DNA binding affinity and docking studies revealed that these new conjugates are DNA interactive topoisomerase I inhibitors.
引用
收藏
页码:4916 / 4929
页数:14
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