Evaluation of mutagenic and antimutagenic properties of new derivatives of pyrrolidine-2,5-dione with anti-epileptic activity, by use of the Vibrio harveyi mutagenicity test.
The Vibrio harveyi test was used to evaluate mutagenic and antimutagenic properties of nineteen new derivatives of pyrrolidine-2,5-dione (compounds 1-19) with antiepileptic activity. Four V. harveyi strains were used: BB7 (wild type) and the genetically modified strains BB7M, BB7X and BB7XM (i.e. strains with additional mucA and mucB genes, UV hypersensitivity, and UV hypersensitivity with plasmid pAB91273, respectively). None of the derivatives of 2-ethyl-2-methylsuccinic acid (compounds 1-7) had mutagenic activity against the tester strains of V. harveyi, but this set had strong or moderate antimutagenic activity against 4-nitroquinoline-N-oxide (NQNO) in the tester strains BB7, BB7X, and BB7M. This antimutagenic activity ranged from 51% to 67%, through 51-66% to 71-83% for V. harveyi BB7, BB7X and BB7M strains, respectively. Mutagenic activities in the group of 2,2-diphenyl-succinic acid derivatives (compounds 8-19) were variable and depended on the tester strain used. Compounds 8-19 were devoid of mutagenic properties against BB7 (wild-type strain). Among this group only compound 9, with the fluorine substituent in position 2 of the aromatic system, was devoid of mutagenic potential against all tester strains. The compounds in this group (8-19) demonstrated strong antimutagenic activity only against strain BB7 (inhibition ranging from 51% to 71%). We conclude that there are various mutagenic and antimutagenic activities of derivatives of pyrrolidine-2,5-dione. Moreover, our studies have proven that the V. harveyi test can be applied for primary mutagenicity and antimutagenicity assessment of these new compounds.
Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University, Medical College, Medyczna 9, 30-688 Kraków, Poland. Electronic address: elzbieta.pekala@uj.edu.pl.
Elżbieta
E
Pękala
Piotr
P
Liana
Paulina
P
Kubowicz
Beata
B
Powroźnik
Jolanta
J
Obniska
Iwona
I
Chlebek
Alicja
A
Węgrzyn
Grzegorz
G
Węgrzyn
D000927:Anticonvulsants / Q000494:pharmacology*; D016587:Antimutagenic Agents / Q000494:pharmacology*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011759:Pyrrolidines / Q000494:pharmacology* / Q000633:toxicity; D014733:Vibrio / Q000187:drug effects / Q000235:genetics
D000927:Anticonvulsants; D016587:Antimutagenic Agents; D009153:Mutagens; D011759:Pyrrolidines; C032519:pyrrolidine
Anticonvulsants; Antimutagenicity assay; Mutagenicity assay; Succinimide; Vibrio harveyi test