title: 3,5-Bis(benzylidene)-1-[3-(2-hydroxyethylthio)propanoyl]piperidin-4-ones: a novel cluster of potent tumor-selective cytotoxins.
abstract: Novel 3,5-bis(benzylidene)-1-[3-(2-hydroxyethylthio)propanoyl]piperidin-4-ones (3a-e) display potent cytotoxicity and a preferential lethality toward various neoplasms compared to some normal cells. The corresponding sulfonic acid analogues 5a-e and an isostere 4 demonstrated substantially lower activity. The leads 3d and 3e possess very high activity against colon cancer and leukemia cell lines, caused DNA fragmentation, and activated caspase-3 in HL-60 cells. The enones 3b-e were well tolerated in a short-term toxicity screen in mice.
authors: Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5C9, Canada. umashankar.das@usask.ca
authors: Umashankar
authors: U
authors: Das
authors: Hari N
authors: HN
authors: Pati
authors: Hiroshi
authors: H
authors: Sakagami
authors: Ken
authors: K
authors: Hashimoto
authors: Masami
authors: M
authors: Kawase
authors: Jan
authors: J
authors: Balzarini
authors: Erik
authors: E
authors: De Clercq
authors: Jonathan R
authors: JR
authors: Dimmock
mesh_terms: D000818:Animals; D001597:Benzylidene Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
chemical_list: D001597:Benzylidene Compounds; D010880:Piperidines; D013440:Sulfides