2. Academic Validation
  3. 3,5-Bis(3-alkylaminomethyl-4-hydroxybenzylidene)-4-piperidones: A Novel Class of Potent Tumor-Selective Cytotoxins

3,5-Bis(3-alkylaminomethyl-4-hydroxybenzylidene)-4-piperidones: A Novel Class of Potent Tumor-Selective Cytotoxins

  • J Med Chem. 2016 Jan 28;59(2):763-9. doi: 10.1021/acs.jmedchem.5b01706.
Subhas S Karki 1,  Umashankar Das 1,  Naoki Umemura 2,  Hiroshi Sakagami 2,  Shoko Iwamoto 2,  Masami Kawase 3,  Jan Balzarini 4,  Erik De Clercq 4,  Stephen G Dimmock 5,  Jonathan R Dimmock 1
Affiliations

Affiliations

  • 1 Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan , Saskatoon, Saskatchewan S7H 5C9, Canada.
  • 2 Department of Diagnostic and Therapeutic Sciences, Division of Pharmacology, Meikai University School of Dentistry , 1-1 Keyakidai, Sakado, Saitama 350-0238, Japan.
  • 3 Faculty of Pharmaceutical Sciences, Matsuyama University , 4-2 Bunkyo-Chu, Matsuyama, Ehime 790-8578, Japan.
  • 4 Rega Institute for Medical Research, Katholieke Universiteit Leuven , B-3000 Leuven, Belgium.
  • 5 Department of Finance, Nanyang Technological University , Singapore 639798, Singapore.
PMID: 26727215 DOI: 10.1021/acs.jmedchem.5b01706
Abstract

Novel 4-piperidone derivatives 2a-f are disclosed as potent cytotoxins. Many of these compounds are more potent than the reference drug melphalan. The compounds in series 2, 4-7 display selective toxicities toward various neoplasms compared to some normal cells. 2a is one of the promising lead molecules that display >11-fold higher growth inhibiting potency than 5-fluorouracil against human colon Cancer cells. 2a induces Apoptosis, DNA fragmentation, and cleavage of poly ADP-ribose polymerase.

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