Özet:

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.

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