Horton, J. K. and Thimmaiah, K. N. and Harwood, F. C. and Kuttesch, J. F. and Houghton, P. J. (1993) Pharmacological characterization of N-substituted phenoxazines directed toward reversing Vinca alkaloid resistance in multidrug-resistant cancer cells. Molecular Pharmacology, 44 (3). pp. 552-559. ISSN 0026-895X
Full text not available from this repository. (Request a copy)Abstract
Previously we reported the synthesis and partial characterization of 21 N-10-substituted phenoxazines in reversing Vinca alkaloid resistance. Here we report on a subset of these compounds; we have compared their activities in increasing Vinca alkaloid accumulation and reversing drug resistance in KB-Ch(R)8-5 and GC3/c1 (human colon carcinoma) cell lines. Results demonstrated that 1) N-substituted phenoxazines increase accumulation of vinblastine; 2) within this series, there is little correlation or ranking of activity between the two cell lines when Vinca alkaloid accumulation is compared at equal concentrations of modulator; 3) N-substituted phenoxazines demonstrate both quantitative and qualitative differences, compared with verapamil, a standard modulator; and 4) the series includes at least two compounds, 10-3'-N-bis(hydroxyethyl)amino]propyl]phenoxazine and 10-(N-piperidinoacetyl)phenoxazine, which increase Vinca alkaloid accumulation but do not significantly inhibit efflux. Additionally, certain of these multidrug resistance modulators significantly enhance accumulation (8-50-fold) of Vinca alkaloids in cell lines with very low or undetectable P-glycoprotein levels, where verapamil has little activity. It is concluded that at least part of the activity of some of these N-substituted phenoxazine modulators may be mediated through a P-glycoprotein-independent mechanism.
| Item Type: | Article |
|---|---|
| Subjects: | B Life Science > Molecular Biology |
| Divisions: | Department of > Molecular Biology |
| Depositing User: | Users 23 not found. |
| Date Deposited: | 06 May 2021 08:29 |
| Last Modified: | 18 Nov 2022 10:31 |
| URI: | http://eprints.uni-mysore.ac.in/id/eprint/16293 |
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