Anti-calmodulin acridone derivatives modulate vinblastine resistance in multidrug resistant (MDR) cancer cells

Hegde, R. and Thimmaiah, P. and Yerigeri, M. C. and Krishnegowda, G. and Thimmaiah, K. N. and Houghton, P. J. (2004) Anti-calmodulin acridone derivatives modulate vinblastine resistance in multidrug resistant (MDR) cancer cells. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 39 (2). pp. 161-177.

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Abstract

Multidrug resistance (MDR) is one of the main obstacles limiting the efficacy of chemotherapy treatment of tumors. Parent acridones 1A and 1B were prepared by the Ullmann reaction followed by cyclization and N-alkylation. N-(omega-Chloroalkyl) analogues were subjected to iodide catalyzed nucleophilic Substitution reaction with secondary amines to get the compounds 3A-13A and 3B-13B, which enhanced the uptake of vinblastine in KBCh(R)-8-5 cells to a greater extent (2.6-13.1-fold relative to control) than verapamil. The study oil the structure-activity relationship revealed that substitution of -H at position C-4 in acridone nucleus by -OCH3 increased the cytotoxic and anti-MDR activities. The ability of acridones to inhibit calmodulin dependent cyclic AMP phosphodiesterase has been determined and the results have shown a strong positive correlation between anti-calmodulin activity and cytotoxicity in KBCh(R)-8-5 cells or anti-MDR activity. (C) 2003 Elsevier SAS. All rights reserved.

Item Type:	Article
Uncontrolled Keywords:	acridones; anti-MDR activity; anti-calmodulin activity
Subjects:	C Chemical Science > Chemistry
Divisions:	Department of > Chemistry
Depositing User:	Users 23 not found.
Date Deposited:	27 Aug 2019 11:37
Last Modified:	27 Aug 2019 11:37
URI:	http://eprints.uni-mysore.ac.in/id/eprint/6615

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