title: Tumour-specific cytotoxicity and structure-activity relationships of novel 1-[3-(2-methoxyethylthio)propionyl]-3,5-bis(benzylidene)-4-piperidones.
abstract: A series of 1-acyl-3,5-bis(benzylidene)-4-piperidones 3-7 were designed and synthesized as novel cytotoxic agents. These compounds displayed potent cytotoxic properties towards human Molt4/C8, CEM, HSC-2, HSC-3 and HSC-4 neoplasms and also to murine L1210 cells. The majority of the compounds have sub-micromolar or very low micromolar IC50 and CC50 values and are significantly more potent than the reference alkylating drug melphalan. Evaluation of these compounds against non-malignant HGF and HPLF cells revealed the tumour-specific toxicity. In particular, 3e emerged as a promising lead cytotoxic agent which caused apoptosis and PARP1 cleavage in HSC-2 cells.
authors.affiliation: Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hossain
authors.affiliation: Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada. Electronic address: umashankar.das@usask.ca.
authors.forename: Umashankar
authors.initials: U
authors.lastname: Das
authors.affiliation: Division of Pharmacology, Mekai University School of Dentistry, Saitama 350-0238, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Umemura
authors.affiliation: Division of Pharmacology, Mekai University School of Dentistry, Saitama 350-0238, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
authors.affiliation: Rega Institute of Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: Rega Institute of Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.affiliation: Faculty of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime 790-8578, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Kawase
authors.affiliation: Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada. Electronic address: jr.dimmock@usask.ca.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dimmock
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D010881:Piperidones / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C526290:3,5-bis(benzylidene)-4-piperidone; D000970:Antineoplastic Agents; D010881:Piperidones
keywords: 4-Piperidone; Cytotoxicity; Structure–activity relationships; Tumour-specific toxicity; α,β-Unsaturated ketone