Indole and 2,4-Thiazolidinedione conjugates as potential anticancer modulators

PeerJ

article

Domenica M. Corigliano¹  Riyaz Syed²  Sebastiano Messineo¹  Antonio Lupia¹  Rahul Patel³  Chittireddy Venkata Ramana Reddy²  Pramod K. Dubey²  Carmela Colica⁴  Rosario Amato¹  Giovambattista De Sarro¹  Stefano Alcaro¹  Adisherla Indrasena²  Antonio Brunetti¹ 

[1] Department of Health Sciences, University “Magna Græcia” of Catanzaro;Department of Chemistry, Jawaharlal Nehru Technological University;Department of Food Science and Biotechnology, Dongguk University;CNR, IBFM UOS of Germaneto, University “Magna Græcia” of Catanzaro

关键词: Thiazolidinediones;    Cancer;    Cellular viability;    Wound healing;    Cell proliferation;    BCL-xL;    Apoptosis;   

DOI  :  10.7717/peerj.5386

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundThiazolidinediones (TZDs), also called glitazones, are five-membered carbon ring molecules commonly used for the management of insulin resistance and type 2 diabetes. Recently, many prospective studies have also documented the impact of these compounds as anti-proliferative agents, though several negative side effects such as hepatotoxicity, water retention and cardiac issues have been reported. In this work, we synthesized twenty-six new TZD analogues where the thiazolidinone moiety is directly connected to an N-heterocyclic ring in order to lower their toxic effects.MethodsBy adopting a widely applicable synthetic method, twenty-six TZD derivatives were synthesized and tested for their antiproliferative activity in MTT and Wound healing assays with PC3 (prostate cancer) and MCF-7 (breast cancer) cells.ResultsThree compounds, out of twenty-six, significantly decreased cellular viability and migration, and these effects were even more pronounced when compared with rosiglitazone, a well-known member of the TZD class of antidiabetic agents. As revealed by Western blot analysis, part of this antiproliferative effect was supported by apoptosis studies evaluating BCL-xL and C-PARP protein expression.ConclusionOur data highlight the promising potential of these TZD derivatives as anti-proliferative agents for the treatment of prostate and breast cancer.

【 授权许可】

CC BY