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Synthesis of N-substituted 3,5-bis(arylidene)-4-piperidones with high antitumor and antioxidant activity.

Abstract
A series of 3,5-bis(arylidene)-4-piperidone (DAP) compounds are considered as synthetic analogues of curcumin for anticancer properties. We performed structure-activity relationship studies by synthesizing a number of DAPs N-alkylated or acylated with nitroxides or their amine precursors as potent antioxidant moieties. Both subtituents on arylidene rings and on piperidone nitrogen (five- or six-membered, 2- or 3-substituted or 3,4-disubstituted isoindoline nitroxides) were varied. The anticancer efficacy of the new DAP compounds was tested by measuring their cytotoxicity to cancer cell lines A2780 and MCF-7 and to the H9c2 cell line. The results showed that all DAP compounds induced a significant loss of cell viability in the human cancer cell lines tested; however, only pyrroline appended nitroxides (5c (Selvendiran, K.; Tong, L.; Bratasz, A.; Kuppusamy, L. M.; Ahmed, S.; Ravi, Y.; Trigg, N. J.; Rivera, B. K.; Kálai, T.; Hideg, K.; Kuppusamy, P. Mol. Cancer Ther. 2010, 9, 1169-1179), 5e, 7, 9) showed limited toxicity toward noncancerous cell lines. Computer docking simulations support the biological activity tested. These results suggest that antioxidant-conjugated DAPs will be useful as a safe and effective anticancer agent for cancer therapy.
AuthorsTamás Kálai, M Lakshmi Kuppusamy, Mária Balog, Karuppaiyah Selvendiran, Brian K Rivera, Periannan Kuppusamy, Kálmán Hideg
JournalJournal of medicinal chemistry (J Med Chem) Vol. 54 Issue 15 Pg. 5414-21 (Aug 11 2011) ISSN: 1520-4804 [Electronic] United States
PMID21702507 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Antioxidants
  • Piperidones
  • Curcumin
Topics
  • Antineoplastic Agents (chemical synthesis, pharmacology)
  • Antioxidants (chemical synthesis, pharmacology)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Computer Simulation
  • Curcumin (analogs & derivatives)
  • Drug Screening Assays, Antitumor
  • Humans
  • Piperidones (chemical synthesis, pharmacology)
  • Structure-Activity Relationship

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