title: 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.
authors.affiliation: Institute of Organic and Medicinal Chemistry, University of Pécs, Pécs, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Kálai
authors.forename: M Lakshmi
authors.initials: ML
authors.lastname: Kuppusamy
authors.forename: Mária
authors.initials: M
authors.lastname: Balog
authors.forename: Karuppaiyah
authors.initials: K
authors.lastname: Selvendiran
authors.forename: Brian K
authors.initials: BK
authors.lastname: Rivera
authors.forename: Periannan
authors.initials: P
authors.lastname: Kuppusamy
authors.forename: Kálmán
authors.initials: K
authors.lastname: Hideg
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D003474:Curcumin / Q000031:analogs & derivatives*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D010881:Piperidones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D010881:Piperidones; D003474:Curcumin