Synthesis and biological evaluation of new benzimidazole-thiazolidinedione hybrids as potential cytotoxic and apoptosis inducing agents

被引：92

作者：

Sharma, Pankaj ^{[1
]}

Reddy, T. Srinivasa ^{[2
]}

Thummuri, Dinesh ^{[3
]}

Senwar, Kishna Ram ^{[1
]}

Kumar, Niggula Praveen ^{[1
]}

Naidu, V. G. M. ^{[3
]}

Bhargava, Suresh K. ^{[2
]}

Shankaraiah, Nagula ^{[1
]}

机构：

[1] NIPER, Dept Med Chem, Hyderabad 500037, Andhra Pradesh, India

[2] RMIT Univ, Sch Sci, CAMIC, GPO BOX 2476, Melbourne, Vic 3001, Australia

[3] NIPER, Dept Pharmacol & Toxicol, Hyderabad 500037, Andhra Pradesh, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 124卷

关键词：

Benzimidazole; Thiazolidinedione; Apoptosis; MitoSOX; Annexin; Cell migration; IN-VITRO; ANTICANCER; DERIVATIVES; DESIGN; BEARING; INHIBITORS; RHODANINE; PATHWAYS; MOIETIES; ANALOGS;

D O I：

10.1016/j.ejmech.2016.08.029

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of new benzimidazole-thiazolidinedione hybrids has been synthesized and evaluated for their cytotoxic potential against a selected human cancer cell lines of prostate (PC-3 and DU-145), breast (MDA-MB-231), lung (A549) and a normal breast epithelial cells (MCF10A). Among the tested compounds, 11p exhibited promising cytotoxicity with IC50 value of 11.46 +/- 1.46 mu M on A549 lung cancer cell line and did not show significant toxicity on normal MCF10A cells. Lung cancer cells (A549) have been used to know the mechanism of cell growth inhibition and apoptosis inducing effect with compound 11p. The treatment of A549 cells with lip showed typical apoptotic morphology like cell shrinkage, chromatin condensation and horseshoe shaped nuclei formation. Flow-cytometry analysis revealed the G2/M phase of cell cycle arrest in a dose dependent manner. Preliminary mechanistic studies suggested that the cell migration was inhibited through the disruption of F-actin protein. Acridine orange-ethidium bromide (AO-EB), DAPI, annexin V-FITC/propidium iodide, rhodamine-123 and MitoSOX assays suggested the induction of apoptosis in A549 cells by compound 11p. (C) 2016 Elsevier Masson SAS. All rights reserved.

引用

页码：608 / 621

页数：14

共 49 条

[1] Synthesis, characterization and antimicrobial activity evaluation of new 2,4-Thiazolidinediones bearing imidazo[2,1-b][1,3,4]thiadiazole moiety [J].

Alagawadi, Kallanagouda R. ;

Alegaon, Shankar G. .

ARABIAN JOURNAL OF CHEMISTRY, 2011, 4 (04) :465-472

[2] 2H-chromene derivatives bearing thiazolidine-2,4-dione, rhodanine or hydantoin moieties as potential anticancer agents [J].

Azizmohammadi, Mohammad ;

Khoobi, Mehdi ;

Ramazani, Ali ;

Emami, Saeed ;

Zarrin, Abdolhossein ;

Firuzi, Omidreza ;

Miri, Ramin ;

Shafiee, Abbas .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2013, 59 :15-22

[3] TIME-RESOLVED FLUORESCENCE OF DAPI IN SOLUTION AND BOUND TO POLYDEOXYNUCLEOTIDES [J].

BARCELLONA, ML ;

CARDIEL, G ;

GRATTON, E .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 170 (01) :270-280

[4] Synthesis and anti-inflammatory activity of new arylidene-thiazolidine-2,4-diones as PPARγ ligands [J].

Barros, Cleiton Diniz ;

Amato, Angelica Amorim ;

de Oliveira, Tiago Bento ;

Rocha Iannini, Karime Bicas ;

da Silva, Anekecia Lauro ;

da Silva, Teresinha Goncalves ;

Leite, Elisa Soares ;

Hernandes, Marcelo Zaldini ;

Alves de Lima, Maria do Carmo ;

Galdino, Suely Lins ;

Rocha Neves, Francisco de Assis ;

Pitta, Ivan da Rocha .

BIOORGANIC & MEDICINAL CHEMISTRY, 2010, 18 (11) :3805-3811

[5] Cucurbitacin B induces apoptosis and S phase cell cycle arrest in BEL-7402 human hepatocellular carcinoma cells and is effective via oral administration [J].

Chan, Kin Tak ;

Meng, Fan Yan ;

Li, Qian ;

Ho, Cheong Yip ;

Lam, Tsz Shan ;

To, Yu ;

Lee, Wai Him ;

Li, Miao ;

Chu, Kee Hung ;

Toh, Melvin .

CANCER LETTERS, 2010, 294 (01) :118-124

[6] New chemotherapeutic agents: Update of major chemoradiation trials in solid tumors [J].

Curran, WJ .

ONCOLOGY, 2002, 63 :29-38

[7] Apoptosis: A review of programmed cell death [J].

Elmore, Susan .

TOXICOLOGIC PATHOLOGY, 2007, 35 (04) :495-516

[8] Promoting apoptosis as a strategy for cancer drug discovery [J].

Fesik, SW .

NATURE REVIEWS CANCER, 2005, 5 (11) :876-885

[9] Targeting cell death signalling in cancer: minimising 'Collateral damage' [J].

Fox, Joanna L. ;

MacFarlane, Marion .

BRITISH JOURNAL OF CANCER, 2016, 115 (01) :5-11

[10] Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy [J].

Fulda, S. ;

Debatin, K. -M .

ONCOGENE, 2006, 25 (34) :4798-4811

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