title: In vitro mutagenic, antimutagenic, and antioxidant activities evaluation and biotransformation of some bioactive 4-substituted 1-(2-methoxyphenyl)piperazine derivatives.
abstract: In vitro mutagenic, antimutagenic, and antioxidant potency evaluation and biotransformation of six novel 4-substituted 1-(2-methoxyphenyl)piperazine derivatives demonstrating antidepressant-like activity were investigated. Mutagenic and antimutagenic properties were assessed using the Ames test; free radical scavenging activity was evaluated with 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay and biotransformation was performed with liver microsomes. It was found that all tested compounds are not mutagenic in bacterial strains TA100 and TA1535 and exhibit antimutagenic effects in the Ames test. Noteworthy, compounds possessing propyl linker between phenoxyl and N-(2-methoxyphenyl)piperazine displayed more pronounced antimutagenic properties than derivatives with ethoxyethyl linker. Additionally, compounds 2 and 6 in vitro biotransformation showed that primarily their hydroxylated or O-dealkylated metabolites are formed. Some of the compounds exhibited intrinsic clearance values lower than those reported previously for antidepressant imipramine. To sum up, the results of the present study might represent a valuable step in designing and planning future studies with piperazine derivatives.
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medycznz Street, 30-688, Krakow, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Słoczyńska
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, 30-688, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Pańczyk
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, 30-688, Poland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Waszkielewicz
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, 30-688, Poland.
authors.forename: Henryk
authors.initials: H
authors.lastname: Marona
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medycznz Street, 30-688, Krakow, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Pękala
mesh_terms: D000818:Animals; D016587:Antimutagenic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology*; D001711:Biotransformation; D001713:Biphenyl Compounds / Q000037:antagonists & inhibitors / Q000737:chemistry; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D016296:Mutagenesis / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity; D010851:Picrates / Q000037:antagonists & inhibitors / Q000737:chemistry; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D019810:Sodium Azide / Q000037:antagonists & inhibitors / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D016587:Antimutagenic Agents; D000975:Antioxidants; D001713:Biphenyl Compounds; D009153:Mutagens; D010851:Picrates; D010879:Piperazines; C040083:1-(2-methoxyphenyl)piperazine; D019810:Sodium Azide; C004931:1,1-diphenyl-2-picrylhydrazyl
keywords: Ames test; antimutagenicity; biotransformation; mutagenicity; piperazine derivatives