title: 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.
abstract: A 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 microM 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.
authors.affiliation: Department of Chemistry, Faculty of Sciences, Ataturk University, 25240, Erzurum, Turkey.
authors.forename: Ebru
authors.initials: E
authors.lastname: Mete
authors.forename: Halise Inci
authors.initials: HI
authors.lastname: Gul
authors.forename: Pakize
authors.initials: P
authors.lastname: Canturk
authors.forename: Zeki
authors.initials: Z
authors.lastname: Topcu
authors.forename: Bulbul
authors.initials: B
authors.lastname: Pandit
authors.forename: Mustafa
authors.initials: M
authors.lastname: Gul
authors.forename: Pui-Kai
authors.initials: PK
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D011407:Propane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology
chemical_list: D010880:Piperidines; D004264:DNA Topoisomerases, Type I; D011407:Propane