Cancer preventive agents 10. Prenylated dehydrozingerone analogs as potent chemopreventive agents

Abstract

Dehydrozingerone analogs and related compounds were screened as potential antitumor promoters by using the in vitro short-term 12-O-tetradecanphorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) activation assay. Among 40 synthesized compounds, the prenylated analogs 16 and 34-36 showed the most significant and promising activity (100% inhibition of activation at 1×10 3 mol ratio/TPA, and 82-80%, 37-35%, 13-11% inhibition at 5×10 2 , 1×10 2 , 1×10 mol ratio/TPA, respectively) in this screening. Their activity profiles were comparable to that of the reference standard curcumin. While a prenyl moiety conferred potent chemopreventive activity, an extended prenyl unit such as a farnesyl moiety did not improve activity. Because in vitro inhibitory effects in this assay generally correlate well with in vivo inhibitory effects on tumor promotion, our results strongly suggested that prenylated 16 and 34-36 are likely to be promising antitumor promoters.

Cancer preventive agents 11. Novel analogs of dimethyl dicarboxylate biphenyl as potent cancer chemopreventive agents†

“…The analogs with prenyl-like unsaturated alkyl groups, such as 12-14, 19, and 20 exhibited relatively high activity. This finding is consistent with other reports that a prenyl-like group tends to enhance the inhibitory effect on EBA activation (Tatsuzaki et al, 2010). The presence of an aromatic ring on the C-2,2′ side chain, as found in 6, 17, and 18, reduced the inhibitory effect on EBV-EA activation.…”

“…In addition, while many 2,2′-carboxylate ester derivatives have been covered in various patents and papers, the modification of a 2,2′-bismethylene alcohol DDB intermediate (21) appears to be a new avenue of exploration. A prenylated side chain, which has been found to be effective in cancer chemoprevention studies of other compound classes (Tatsuzaki et al, 2010), was a logical first choice. In addition, short unsaturated fatty acid chains, which have resulted in good chemopreventive activity in betulinic acid derivatives, were included in our modification scheme (Nakagawa-Goto et al, 2009).…”

Anti-tumour-promoting and thermal-induced protein denaturation inhibitory activities of β-sitosterol and lupeol isolated from Diospyros lotus L.

“…The EBV-EA induced by TPA in Raji cells is frequently used for the assessment of the antitumour-promoting activity (Tatsuzaki et al 2010;Maoka et al 2012). The results of our study reflect significant anti-tumour-promoting effect of the compounds by showing potent inhibitory effect against TPA (20 ng/32 pmol)-induced EBV-EA activation in Raji cells (8.2% and 6.9% induction of EBV-EA at 100 mg/ml concentration, respectively).…”

Cytotoxic and Antimicrobial Activity of Dehydrozingerone based Cyclopropyl Derivatives

“…O ‐Alkyl dehydrozingerones were synthesized following described procedures . The chemical synthesis of compounds 2a – 2d and 2f – 2i was published earlier . Isobutyl derivative 2e and methallyl derivative 2j are new compounds and their structure and spectral data are already given.…”

“…[44 -46] The chemical synthesis of compounds 2a -2d and 2f -2i was published earlier. [47] Isobutyl derivative 2e and methallyl derivative 2j are new compounds and their structure and spectral data are already given. Out of the products of type 3, only compound 3a was earlier described, [48] whereas 3b -3j are new compounds, prepared according described procedure [5] (Scheme 1).…”