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

T. Kalai, M. Lakshmi Kuppusamy, Mária Balog, Karuppaiyah Selvendiran, Brian K. Rivera, Periannan Kuppusamy, K. Hideg

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)5414-5421
Number of pages8
JournalJournal of Medicinal Chemistry
Volume54
Issue number15
DOIs
Publication statusPublished - Aug 11 2011

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Piperidones
Antioxidants
Cell Line
Neoplasms
Curcumin
Structure-Activity Relationship
Computer Simulation
Antineoplastic Agents
Amines
Cell Survival
Nitrogen

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Synthesis of N-substituted 3,5-bis(arylidene)-4-piperidones with high antitumor and antioxidant activity. / Kalai, T.; Kuppusamy, M. Lakshmi; Balog, Mária; Selvendiran, Karuppaiyah; Rivera, Brian K.; Kuppusamy, Periannan; Hideg, K.

In: Journal of Medicinal Chemistry, Vol. 54, No. 15, 11.08.2011, p. 5414-5421.

Research output: Contribution to journalArticle

Kalai, T. ; Kuppusamy, M. Lakshmi ; Balog, Mária ; Selvendiran, Karuppaiyah ; Rivera, Brian K. ; Kuppusamy, Periannan ; Hideg, K. / Synthesis of N-substituted 3,5-bis(arylidene)-4-piperidones with high antitumor and antioxidant activity. In: Journal of Medicinal Chemistry. 2011 ; Vol. 54, No. 15. pp. 5414-5421.
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