Thirty-four glutathione conjugates of 5,8-dimethoxy-1,4-naphthoquinones (DMNQ) were synthesized and their structure was determined. The yield of GSH conjugate was dependent on size of alkyl group; the longer the size of alkyl group was, the lower was the yield. It was also found that the length of alkyl side chain influenced the chemical shift of quinonoid protons; the quinonoid protons of 2-glutathionyl DMNQ derivatives with R=H to propyl, 6.51–6.59 ppm vs. other ones with R=butyl to heptyl, 6.64–6.68 ppm. This was explained to be due to a folding effect of longer alkyl group. Glutathione (GSH) reacted with DMNQ derivative first to form a 1,4-adduct (2- or 3-glutathionyl-1,4-dihydroxy-5,8-dimethoxynaphthalenes) and then, the adduct was autooxidized to 2- or 3-glutathionyl-DMNQ derivatives. Moreover, GSH reduced DMNQ derivatives to their hydrogenated products. It was suggested that such an organic reaction might play an important role for a study of metabolism or toxicity of DMNQ derivatives in the living cells.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Ahn, B. Z., Baik, K. U., Kweon, G. R., Lim, K. and Hwang, B. D., Acylshikonin analogues: Synthesis and inhibition of DNA topoisomerase I.J. Med. Chem., 38(6), 1044–1047 (1995).
Baik, K. U., Song, G. Y., Kim, Y., Sok, D. E. and Ahn, B. Z., Substituted Naphthazarins: Synthesis and Antitumor Activity.Arch. Pharm. Med. Chem., 330, 377–382 (1997).
Belisario, M. A., Pecce, R., Maturo, M., De Rosa, S., Arylation of sulfhydryl groupsin vitro by the naturally occuring sesquiterpenoid benzoquinone avarone.Toxicology, 86, 89–108 (1994).
Gant, T. W., Rao, D. N. R., Mason, R. P. and Cohen, G. M. Redox cycling and sulfhydryl arylation: their relative importance in the mechanism of quinone cytotoxicity to isolated hepatocytes.Chem Biol. Interact., 65, 157–173 (1988).
Hissin P. J. and Hilf, R., A fluorometric method for determination of oxidized and reduced glutathione in tissues.Anal. Biochem., 74, 214–226 (1976).
Hyslop, P. A. and Sklar, L. A., A quantitative fluorimeric assay for the determination of oxidant production by polymorphonuclear leukocytes: Its use in the simultaneous fluorimetric assay of cellular activation processes.Anal. Biochem., 141, 280–286 (1984).
Leo, A., Hansch, C. and Elkins, D., Partition coefficients and their uses.Chem. Rev., 71, 525 (1971).
Moore, R. E. and Scheuer, P. J., Nuclear magnetic resonance spectra of substituted naphthoquinones. Influence of substitution on tautomerism, anisotropy, and stereochemistry in the naphthazarin system.J. Org. Chem., 31, 3272–3283 (1966).
You, Y. J., Zheng, X. G., Kim Y. and Ahn B. Z., Naphthazarin derivatives; synthesis, formation of glutathione conjugate, inhibition of DNA topoisomerase-I and antitumor activity.Arch. Pharm. Res., 21(5), 595–598 (1998).
About this article
Cite this article
Zheng, X., Kang, J., Kim, Y. et al. Glutathione conjugates of 2- or 6-substituted 5,8-dimethoxy-1,4-naphthoquinone derivatives: Formation and structure. Arch Pharm Res 22, 384 (1999). https://doi.org/10.1007/BF02979062
- 5,8-Dimethoxy-1,4-naphthoquinone derivatives
- Glutathione conjugates