Biological Activity of 1-Aryl-3-phenethylamino-1-propanone Hydrochlorides and 3-Aroyl-4-aryl-1-phenethyl-4-piperidinols on PC-3 Cells and DNA Topoisomerase I Enzyme

WOS: 000288580900003PubMed ID: 21319705A number of studies reported Mannich bases to manifest antimicrobial, cytotoxic, anticancer, anti-inflammatory, and anticonvulsant activities. A considerable number of therapeutically important cytotoxic compounds are active on DNA topoisomerases that regulate the DNA topology. In the present study we evaluated the biological activity of mono-Mannich bases, 1-aryl-3-phenethylamino-1-propanone hydrochlorides (1a-10a), and semicyclic mono-Mannich bases, 3-aroyl-4-aryl-1-phenethyl-4-piperidinols (1b-9b), synthesized in our laboratory. We employed androgen-independent human prostate cancer cells (PC-3) to assess the cytotoxicity of the compounds and extended the biological activity evaluation to cover supercoil relaxation assays of mammalian type I topoisomerases. Our results showed that the compounds had cytotoxicity within the 8.2-32.1 mu m range, while two compounds gave rise to a comparable average value in topo I interference of 42% and 40% for 10a (with a hydroxy substituent on the phenyl ring from mono-Mannich bases) and 5b (with a fluoro substituent on the phenyl ring from the semicyclic mono-Mannich base series, piperidinols), respectively.Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TBAG108T548]; Research Foundation of Ataturk University, Erzurum, TurkeyAtaturk University [2006/96, 2007/225]This study was supported by grants from The Scientific and Technological Research Council of Turkey (Grant No. TBAG108T548) to Z. T. and from Research Foundation of Ataturk University, Erzurum, Turkey (Grant No. 2006/96, 2007/225) to H. I. G. The authors thank Dr. Mustafa Arik for the calculations of the Log P values