title: Evaluation of the mutagenic and genotoxic effects of the ALC67 thiazolidine compound in Salmonella strains and human lymphocytes in vitro.
abstract: ALC67 is an N-acylated thiazolidine compound with promising anticancer activity that led to the recent discovery of a series of 3-propionyl thiazolidine-4-carboxylic acid ethyl esters as a family of novel antiproliferative agents. Since the mutagenic and genotoxic properties of marketed anticancer molecules constitute a main issue to be addressed, this study focused on the analysis of the mutagenicity, antimutagenecity, and genotoxicity of this molecule. The mutagenicity and antimutagenicity of ALC67 were evaluated by Ames test performed on Salmonella TA98 and TA100 strains. The genotoxicity of this molecule was investigated in the chromosomal aberration assay on human lymphocytes. All results revealed that the analyzed structure is not mutagenic in the two Salmonella strains tested and was not genotoxic in human lymphocytes in vitro On the other hand, it showed a weak antimutagenic effect in these two bacterial strains. The above results indicate that after performing some more mutagenicity assays using the other recommended strains, this compound can be safely used for the development of new structures exhibiting anticancer activities.
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Yeditepe University, Atasehir, Istanbul, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Charehsaz
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Yeditepe University, Atasehir, Istanbul, Turkey.
authors.forename: F E
authors.initials: FE
authors.lastname: Onen-Bayram
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Yeditepe University, Atasehir, Istanbul, Turkey.
authors.forename: H
authors.initials: H
authors.lastname: Sipahi
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Yeditepe University, Atasehir, Istanbul, Turkey.
authors.forename: K
authors.initials: K
authors.lastname: Buran
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Yeditepe University, Atasehir, Istanbul, Turkey Molecular and Human Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India.
authors.forename: A K
authors.initials: AK
authors.lastname: Giri
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Yeditepe University, Atasehir, Istanbul, Turkey ahmet.aydin@yeditepe.edu.tr.
authors.forename: A
authors.initials: A
authors.lastname: Aydin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D009152:Mutagenicity Tests; D017207:Rats, Sprague-Dawley; D012475:Salmonella / Q000187:drug effects* / Q000235:genetics; D053778:Thiazolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D053778:Thiazolidines
keywords: ALC67; antimutagenicity assay; genotoxicity; in vitro chromosomal aberration assay; mutagenicity assay; novel antiproliferative agent