title: Preliminary mutagenicity and genotoxicity evaluation of selected arylsulfonamide derivatives of (aryloxy)alkylamines with potential psychotropic properties.
abstract: Determination of the mutagenic and genotoxic liability of biologically active compounds is of great concern for preliminary toxicity testing and drug development. In this study, we focused on the evaluation of the mutagenic and genotoxic effects of selected arylsulfonamide derivatives of aryloxyethyl piperidines and pyrrolidines (1-8), classified as 5-HT7 receptor antagonist with antidepressant and procognitive properties, using in silico and in vitro methods: the Vibrio harveyi assay and the SOS/umu-test (umuC Easy CS test). Finally, the antimutagenic potential of tested compounds was evaluated with the V. harveyi assay. It was demonstrated that none of the examined compounds produced a positive response in in vitro assays and these results were in line with in silico prediction. Additionally, all the tested compounds demonstrated various antimutagenic potential, with compound 1 (5-chloro-N-((1-(2-phenoxyethyl)piperidin-4-yl)methyl)thiophene-2-sulfonamide) being the most active against NQNO-induced mutagenicity.
authors.affiliation: Department of Pharmaceutical Biochemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Krakow, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Powroźnik
authors.affiliation: Department of Pharmaceutical Biochemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Krakow, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Słoczyńska
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Krakow, Poland.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Canale
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Grychowska
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Krakow, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Zajdel
authors.affiliation: Department of Pharmaceutical Biochemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Krakow, Poland. elzbieta.pekala@uj.edu.pl.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Pękala
mesh_terms: D016587:Antimutagenic Agents / Q000737:chemistry*; D004249:DNA Damage; D015394:Molecular Structure; D009152:Mutagenicity Tests; D010879:Piperazines / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists / Q000737:chemistry*; D018675:Toxicity Tests; D014733:Vibrio
chemical_list: D016587:Antimutagenic Agents; D010879:Piperazines; D011759:Pyrrolidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C104425:serotonin 7 receptor
keywords: 5-HT7 receptor antagonists; Anti/mutagenesis; Genotoxicity; SOS response; SOS/umu-test; Salmonella typhimurium (TA1535/pSK1002); Vibrio harveyi assay