Synthesis and biological evaluation of 5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one structural derivatives as anti-cancer and apoptosis inducing agents

被引：62

作者：

Kumar, Chintakunta Praveen ^{[1
,2
,3
]}

Reddy, T. Srinivasa ^{[1
,4
,5
,6
]}

Mainkar, Prathama S. ^{[3
]}

Bansal, Vipul ^{[1
,4
,5
]}

Shukla, Ravi ^{[1
,4
,5
,6
]}

Chandrasekhar, Srivari ^{[3
]}

Huegel, Helmut M. ^{[1
]}

机构：

[1] RMIT Univ, Sch Appl Sci, GPO Box 2476, Melbourne, Vic 3001, Australia

[2] IICT RMIT Res Ctr SIR Indian Inst Chem Technol, Hyderabad 500007, Andhra Pradesh, India

[3] CSIR IICT, Div Nat Prod Chem, Hyderabad 500007, Andhra Pradesh, India

[4] RMIT Univ, Hlth Innovat Res Inst, Bundoora, Vic 3083, Australia

[5] RMIT Univ, Sch Appl Sci, NanoBiotechnol Res Lab, Ian Potter NanoBioSensing Facil, Melbourne, Vic 3000, Australia

[6] RMIT Univ, Ctr Adv Mat & Ind Chem, Melbourne, Vic 3000, Australia

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 108卷

关键词：

Dibenzodiazepinones; Triazoles; Anti-cancer activity; Apoptosis; PHARMACOLOGICAL EVALUATION; IDENTIFICATION; POTENT; CLOZAPINE; CURCUMIN; NITROGEN; ANALOGS; DESIGN; OXYGEN; CELLS;

D O I：

10.1016/j.ejmech.2015.12.007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of thirteen 5H-dibenzo [b,e][1,4]diazepin-11(10H)-one structural derivatives has been synthesized and evaluated for anti-proliferative activity against five human cancer cell lines. Compound 9a exhibited potent tumour growth inhibition in all cell lines with IC50 values in the range of 0.71-7.29 mu M. Experiments on lung (A549) and breast (MDAMB-231) cancer cell lines to investigate the mechanisms of growth inhibition and apoptosis inducing effects of 9a showed that it arrested both cancer cell lines in the G2/M phase of cell cycle in a dose dependent manner. Hoechst staining analysis revealed that 9a inhibited tumour cell proliferation through apoptosis induction. Additionally, the mitochondria! membrane potential (Delta Psi m) was affected and the levels of reactive oxygen species (ROS) were raised. The simple synthetic preparation and their biological properties make these dibenzodiazepinone-triazole scaffolds promising new entities for the development of cancer therapeutics. (C) 2015 Elsevier Masson SAS. All rights reserved.

引用

页码：674 / 686

页数：13

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