2. Academic Validation
  3. 3,5-Bis(benzylidene)-1-[3-(2-hydroxyethylthio)propanoyl]piperidin-4-ones: a novel cluster of potent tumor-selective cytotoxins

3,5-Bis(benzylidene)-1-[3-(2-hydroxyethylthio)propanoyl]piperidin-4-ones: a novel cluster of potent tumor-selective cytotoxins

  • J Med Chem. 2011 May 12;54(9):3445-9. doi: 10.1021/jm101595p.
Umashankar Das 1,  Hari N Pati,  Hiroshi Sakagami,  Ken Hashimoto,  Masami Kawase,  Jan Balzarini,  Erik De Clercq,  Jonathan R Dimmock
Affiliations

Affiliation

  • 1 Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5C9, Canada. [email protected]
PMID: 21449610 DOI: 10.1021/jm101595p
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.

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