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3,5-Bis(benzylidene)-1-[3-(2-hydroxyethylthio)propanoyl]piperidin-4-ones: A Novel Cluster of Potent Tumor-Selective Cytotoxins

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journal contribution
posted on 12.05.2011, 00:00 authored by Umashankar Das, Hari N. Pati, Hiroshi Sakagami, Ken Hashimoto, Masami Kawase, Jan Balzarini, Erik De Clercq, Jonathan R. Dimmock
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 5ae 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 3be were well tolerated in a short-term toxicity screen in mice.