1. Academic Validation
  2. Novel 2,4- thiazolidinediones: Synthesis, in vitro cytotoxic activity, and mechanistic investigation

Novel 2,4- thiazolidinediones: Synthesis, in vitro cytotoxic activity, and mechanistic investigation

  • Eur J Med Chem. 2017 Jun 16:133:340-350. doi: 10.1016/j.ejmech.2017.03.052.
Kamel Metwally 1 Harris Pratsinis 2 Dimitris Kletsas 2
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt. Electronic address: kametwally@hotmail.com.
  • 2 Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre of Scientific Research "Demokritos", Athens, Greece.
Abstract

Two thiazolidinedione scaffolds different in the position of the thiazolidinedione ring in the molecule were tested for in vitro cytotoxic activity in a panel of human Cancer cell lines namely, prostate Cancer cells PC-3, breast carcinoma cells MDA-MB-231, and fibrosarcoma cells HT-1080. Some of the target compounds of the A-series where the thiazolidinedione ring is terminal, displayed cytotoxic activity in the low micromolar range in the cell lines tested. Target thiazolidinediones of the B-series where the thiazolidinedione ring is located in the middle of the molecule showed cytotoxic activity comparable to that of their A-series counterparts. Our mechanistic studies indicated that the most cytotoxic compounds in this study have pro-apoptotic capacity. Key signaling mechanisms were investigated and found to vary depending on the target cell context, in line with previous observations regarding thiazolidinediones.

Keywords

Anticancer; Apoptosis; The glitazones; Thiazolidinediones.

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