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

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.

• Authors: Subhas S Karki, Umashankar Das, Naoki Umemura, Hiroshi Sakagami, Shoko Iwamoto, Masami Kawase, Jan Balzarini, Erik De Clercq, Stephen G Dimmock, Jonathan R Dimmock
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 59 Issue 2 Pg. 763-9 (Jan 28 2016) ISSN: 1520-4804 [Electronic] United States
• PMID: 26727215 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Antineoplastic Agents
• Antineoplastic Agents, Alkylating
• Benzylidene Compounds
• Cytotoxins
• Piperidones
• Poly(ADP-ribose) Polymerases
• Melphalan
• Fluorouracil

Topics

• Animals
• Antimetabolites, Antineoplastic (pharmacology)
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Antineoplastic Agents, Alkylating (pharmacology)
• Apoptosis (drug effects)
• Benzylidene Compounds (chemical synthesis, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cytotoxins (chemical synthesis, pharmacology)
• DNA Fragmentation (drug effects)
• Drug Screening Assays, Antitumor
• Fluorouracil (pharmacology)
• Humans
• Melphalan (pharmacology)
• Mice
• Piperidones (chemical synthesis, pharmacology)
• Poly(ADP-ribose) Polymerases (drug effects)
• Structure-Activity Relationship