Preferential cytotoxicity of caffeic acid phenethyl ester analogues on oral cancer cells
Introduction
Recently we synthesized [1] and studied [2] the constituents of natural honey-propolis, which is a folk medicine employed for treating various ailments. We assayed them in peripheral blood mononuclear cells (PBMC) infected by M-tropic (JRCSF), T-tropic (NL-4-3), and Dual tropic (89.6) of HIV-1 isolates. Caffeic acid phenethyl ester (CAPE) and caffeic acid methyl ester (MC) showed significant inhibition on the growth of HIV-replication in PBMC cells. 3-(3,4-Dimethoxy-phenyl)-acrylic phenethyl ester (PEDMC) showed less inhibition effect than CAPE or MC. CAPE-like analogues exhibited a broad spectrum of medical applications including antibiotic, antiviral, anti-inflammatory, and tumor growth inhibition [3], [4], [5]. Furthermore, Rao et al. have shown that CAPE has chemoprevention [6], [7], [8], [9], [10] and antitumor properties [11], [12]. Since the biological properties of propolis and its constituent compounds have become a point of particular interest, and extraction of these compounds required large quantities of propolis, we have designed and undertaken the synthesis of nine CAPE-like analogues for investigating oral cancer.
The commercial availability of caffeic acid prompted us to prepare some caffeic acid esters from this compound. However, selective esterification of the α, β-unsaturated carboxyl group presents a problem because of the solubility of caffeic acid. Although CAPE (1) has been synthesized by several groups [7], [13], [14], their preparations gave only poor yields of the target compound and the synthetic approaches are very time consuming and complicated. To overcome these technical difficulties, we have found that CAPE and its derivatives can be easily prepared in a one pot reaction in high yield (86%) [15].
We report herein the effect of nine agents on the growth of normal human buccal mucosal fibroblast (BF), oral submucosus fibroblast (OSF), neck metastasis of Gingiva carcinoma (GNM), tongue squamous cell carcinoma (TSCCa) cells using the MTT assay. Differential cytotoxicity was observed in BF versus GNM and TSCCa cell lines in the presence of nine synthetic CAPE-like analogues.
Section snippets
Chemicals
Phenethyl 3-(3,4-dihydroxyphenyl)acrylate (CAPE), phenethyl 3-(3,4-dimethoxyphenyl)acrylate (PEDMC), methyl 3-(3,4-dihydroxyphenyl)acrylate (MC), ethyl 3-(3,4-dihydroxyphenyl)acrylate (EC), phenethyl 3-(4-bromophenyl)acrylic (BrCAPE), ethyl 3-(3,4-dimethoxyphenyl)acrylate (6), ethyl 3-(4-methoxyphenyl)acrylate (7) were synthesized by our developed procedure. Ethyl 2,3-dibromo-3-(3,4-dimethoxyphenyl) propiolate (8) and ethyl 2,3-dibromo-3-(4-methoxyphenyl) propiolate (9) were prepared by a
Results and discussion
Our previous synthetic method was performed with nitrobenzene to provide CAPE in 50% yield. It was worth noting that although reactions described could be regarded, as straightforward, manipulations were sometimes difficult due to the synthesis and solubility of the acid chloride. In addition, there are health risks from toxic solvents, such as benzene and nitrobenzene. Furthermore the methods required substantial amounts of alcohol, reagents, and solvents for esterification. To overcome these
Acknowledgements
The authors are indebted to Dentist Yi-Chao Chang for the generous gift of BF, OSF, GNM and TSSCa cells. For financial support, we thank the National Science Council of the Republic of China (Research Grant NSC 87-2113-M-040-001).
References (18)
- et al.
Effect of caffeic acid esters on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth
Chem.-Biol. Interac.
(1992) - et al.
Inhibitory effect of caffeic acid phenethyl ester on human leukemia
Cancer Lett.
(1996) - et al.
Enantioselective catalytic epoxidation of cinnamate esters
Tetrahedron
(1994) - et al.
Inhibition of HIV-1 integrase by flavones, caffeic acid phenethyl ester (CAPE) and related compounds
Biochem Pharmacol.
(1994) - et al.
Synthesis of caffeic acid esters as antioxidants by esterification via acyl chlorides
Chin. Pharmacol. J.
(1999) - C.C. Yang, New target for anti-retroviral therapy, Abstracts of AIDS Symposium at Chung Shan, Taiwan, February...
- et al.
Antibacterial activity of propolis some of is compounds and their analogs
Pharmazie
(1993) - et al.
Bactericidal effect of propolis in vitro against agents causing upper respiratory tract infections
Arzneim.-Forsch.
(1993) - et al.
Mechanisms involved in the antiinflammatory effect of propolis extract
Drugs Exp. Clin. Res.
(1993)