title: Novel 2,4- thiazolidinediones: Synthesis, in vitro cytotoxic activity, and mechanistic investigation.
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.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt. Electronic address: kametwally@hotmail.com.
authors.forename: Kamel
authors.initials: K
authors.lastname: Metwally
authors.affiliation: Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre of Scientific Research "Demokritos", Athens, Greece.
authors.forename: Harris
authors.initials: H
authors.lastname: Pratsinis
authors.affiliation: Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre of Scientific Research "Demokritos", Athens, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kletsas
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione
keywords: Anticancer; Apoptosis; The glitazones; Thiazolidinediones