Editor-in-Chief İlkay Küçükgüzel Associate Editor Esra Tatar Online ISSN 2630-6344 Publisher Marmara University Frequency Bimonthly (Six issues / year) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Marmara Pharmaceutical Journal 2015 , Vol 19 , Issue 2
The interference of piperidinopropionaphthone hydrochloride in mammalian type I and type II DNA topoisomerase reactions
Huseyin ISTANBULLU1,Sevil ZENCIR2,Agnes BERENYI3,Pakize CANTURK KILICKAYA4,Istvan ZUPKO3,Ercin ERCIYAS1,Zeki TOPCU5
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, EgeUniversity, Izmir, 35100, Turkey
2Department of Medical Biology, Faculty of Medicine, Pamukkale University, Denizli 20070, Turkey
3Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, H-6270, Hungary
4Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Cumhuriyet University, Sivas, 58140, Turkey
5Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Ege University, Izmir, 35100, Turkey
DOI : 10.12991/mpj.2015199638 Majority of anti-cancer drugs were shown to exert their activities by interfering with DNA topoisomerase reactions. Since the identification of Camptothecin as the topoisomerase I targeting compound, these enzymes are widely utilized in biological assays to assess the pharmaceutical significance of the synthetic and natural agents. Because a considerable number of compounds were shown to have cytostatic activities via blocking topoisomerase reactions, we aimed to identify if the previously-reported physiological activities of acetonapthones involves the interference with topoisomerase reactions. We covered topoisomerase activity and cytostatic activity evaluation of piperidinopropionaphthone hydrochloride type Mannich base (MB) to compare its bioactivities to the starting propionaphtone in order to assess the contribution of aminomethyl moiety of the compound on its bioactivity. MB was synthesized and characterized in our laboratory. Supercoiled plasmid relaxation and decatenation assays were carried out to evaluate their biological activities in mammalian DNA topoisomerases. We also assayed the cytostatic activities using HeLa, MCF7 and A431 cell lines. Our data showed a considerable inhibition of MB on type I and type II DNA topoisomerases without a correlation to cytostatic assays. MB exerted a modest activity against the proliferation of MCF7 cells with an IC50 value of 27.62 μM. The presence of MB inhibited topo II decatenation activity as well. Results offer no direct explanation for the contradictory effects on the DNA topoisomerases and the proliferation of cancer cells in vitro. Our results are discussed in relation to potential significance of aminomethyl group of Mannich base in the course of drug-development studies. Keywords : Mannich base, Anti-cancer drugs, Decatenation, Topoisomerase I, Topoisomerase II
Marmara University