Synthesis, cytotoxicity against human oral cancer KB cells and structure-activity relationship studies of trienone analogues of curcuminoids.

Bioorganic & Medicinal Chemistry Letters (Impact Factor: 2.33). 05/2014; DOI: 10.1016/j.bmcl.2014.04.105
Source: PubMed

ABSTRACT A general method for the synthesis of substituted (1E,4E,6E)-1,7-diphenylhepta-1,4,6-trien-3-ones, based on the aldol condensations of substituted 4-phenylbut-3-en-2-ones and substituted 3-phenylacrylaldehydes, was achieved. The natural trienones 4 and 5 have been synthesized by this method, together with the trienone analogues 9-20. These analogues were evaluated for their cytotoxic activity against human oral cancer KB cell line. The structure-activity relationship study has indicated that the analogues with the 1,4,6-trien-3-one function are more potent than the curcuminoid-type function. Analogues with meta-oxygen function on the aromatic rings are more potent than those in the ortho- and para-positions. Free phenolic hydroxy group is more potent than the corresponding methyl ether analogues. Among the potent trienones, compounds 11, 18 and 20 were more active than the anticancer drug ellipticine. All compounds were also evaluated against the non-cancerous Vero cells and it was found that compounds 11, 12 and 17 were much less toxic than curcumin (1); they showed high selectivity indices of 35.46, 33.46 and 31.68, respectively. These analogues are regarded as the potent trienones for anti-oral cancer study.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aminomethyl derivatives of 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one, designed as new cytotoxins, were synthesized and evaluated in terms of their cytotoxic activities. The compounds have low CC50 values in the low micromolar range against HL-60 neoplasms and HSC-2, HSC-3 and HSC-4 carcinoma cells. In general, the average CC50 values of these compounds were higher towards HGF, HPC and HPLF non-malignant cells, which reveals the tumour-selectivity of these aminomethyl derivatives, Mannich bases. Using specific concentrations of compounds 4 and 6 caused cleavage of PARP1 in HSC-2 cells but not HGF cells, which may be a contributing factor to cytotoxicities and the tumour-selectivities.
    Journal of Enzyme Inhibition and Medicinal Chemistry 07/2014; · 2.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is no doubt that diet could eff ectively improve health and halt cancers. Dietary phytochemical compounds and their derivatives represent a cornucopia of eff ectively anticancer compounds. This review discusses existing data on the anticancer activities of curcumin, and then off ers possible explanations for and mechanisms of its cancer-preventive action. This review also off ers insights into the molecular mechanism and targets through which curcumin modulates cell cycle, apoptotic signals, anti-apoptotic proteins, miRNAs, Wnt/beta-catenin signaling, protein kinases, nuclear factor-κB, proteasome activation, epigenetic regulation including DNA methylation and histone modifi cation. Finally, this review provides explanations for how curcumin reverses the multi-drug resistance (MDR) of cancer cells.
    Interventional Medicine and Applied Science. 12/2014; 6(4):139-146.