Abstract
Synthesized 5-arylamino-2-methyl-4,7-dioxobenzothiazoles3a-3o were evaluated for modulation of NAD(P)H: quinone oxidoreductase (NQO1) activity with the cytosolic fractions derived from cultured human lung cancer cells and their cytotoxicity in cultured several human solid cancer cell lines. The 4,7-dioxobenzothiazoles affected the reduction potential by NQO1 activity and showed a potent cytotoxic activity against human cancer cell lines. The tested compounds3a, 3b, 3g, 3h, 3n and3o were considered as more potent cytotoxic agents, and comparable modulators of NQO1 activity.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Beall, H. D., Liu, Y., Siegel, D., Bolton, E. M., Gilson, N. W. and Ross, D., Role of NAD(P)H: quinone oxidoreductase (DT-diaphorase) in cytotoxicity and induction of DNA damage by streptonigrin.Biochem. Pharmacol., 51, 645–652 (1996).
Beall, H. D., Murphy, A. M., Siegel, D., Hargreaves, R. H. J., Butler, J., and Ross, D., Nicotinamide adenine dinucleotide (Phosphate): Quinone oxidoreductase (DT-diaphorase) as a target for bioreductive antitumor quinones: quinone cytotoxicity and selectivity in human lung and breast cancer cell lines.Mol. Pharmacol., 48, 499–504 (1995).
Bradford, M. M., A rapid and sensitive method for the quantitation of microgram quantities of protein using the principle of protein-dye binding.Anal. Biochem., 72, 248–254 (1976).
Ernster, L., DT-diaphorase.Methods Enzymol., 10, 309–317 (1967).
Fryatt, T., Goroski, D. T., Nilson, Z. D., Moody, C. J. and Beall, H. D., Novel quinolinequinone antitumor agents: structure-metabolism studies with NAD(P)H: quinone oxidoreductase (NQO1).Bioorg. Med. Chem. Lett., 9 (15), 2195–2198 (1999).
Lee, S. K., Cui, B., Metha, R. R., Kinghorn, A. D. and Pezzuto, J. M., Cytostatic mechanism and antitumor potential of novel 1H-cyclopenta[b]benzofuran lignans isolated fromAglaia elliptica.Chem.-Biol. Interact., 115, 215–228 (1998).
Phillips, R. M., Inhibition of DT-diaphorase [NAD(P)H: quinone oxidoreductase, EC 1.6.99.2] by 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and flavone-8-acetic acid (FAA): implications for bioreductive drug development.Biochem. Pharmacol., 58, 303–310 (1999).
Rao, K. V. and Beach, J. W., Streptonigrin and related compounds 5. Synthesis and evaluation of some isoquinolin analogues.J. Med. Chem., 34, 1871–1879 (1991).
Rao, K. V. and Rock, C. P., Streptonigrin and related compounds. 6. Synthesis and activity of some quinoxaline analogues.J. Heterocycl. Chem., 33, 447–458 (1996).
Ryu, C. K., Lee, I. K., Jung, S. H. and Lee, C. O., Synthesis and cytotoxic activities of 6-chloro-7-arylamino-5,8-isoquinolinediones.Bioorg. Med. Chem. Lett., 9(8), 1075–1080 (1999).
Ryu, C. K., Lee, Kang, H. Y., Lee, S. K., Nam, K. A., Hong, C. Y., Ko, W. G. and Lee, B. H., 5-Arylamino-2-methyl-4,7-dioxobenzothiazoles as inhibitors of cyclin-dependent kinase 4 and cyctotoxic agents.Bioorg. Med. Chem. Lett., 10(5), 461–464 (2000).
Shaikh, I. A., Johnson, F. and Grollman, A. P., Structure-activity relationship among simple bicyclic analogues. Rate dependent of DNA degradation on quinone reduction potential.J. Med. Chem., 29, 1329–1340 (1986).
Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, T. W., Bokesch, H., Kenney, S. and Boyd, M. R., New colorimetric cytotoxicity assay for anticancer-drug screening.J. Natl. Cancer Inst., 82, 1107–1112 (1990).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ryu, CK., Jeong, HJ., Lee, S.K. et al. Modulation of NAD(P)H:Quinone oxidoreductase (NQO1) activity mediated by 5-arylamino-2-methyl-4,7-dioxobenzothiazoles and their cytotoxic potential. Arch Pharm Res 23, 554–558 (2000). https://doi.org/10.1007/BF02975239
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02975239