jm101595p_si_001.pdf (92.86 kB)

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

Download (92.86 kB)
journal contribution
posted on 12.05.2011 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.

History

Exports