Abstract
Over the past two decades, a number of chemical entities have been investigated in the continuing quest to reverse P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in cancer cells and some have undergone clinical trials, but currently none are in clinical use. Unfortunately, most of these agents suffer clinically from their intrinsic toxicity or from undesired effects on the pharmacokinetics of the accompanying anti-cancer drugs. An acridonecarboxamide (GF120918), Imidazo acridone (C1311) and timethylene acridone derivative 1,3-bis(9-oxoacridin-10-yl)-propane (PBA) have already been shown to be among the group of compounds known to modify P-gp mediated MDR in cancer. In the recent past it has been identified that various N10-substituted acridones can reverse the multidrug resistance (MDR) in cancer by selectively inhibiting the multidrug resistance associated protein (MRP) and calmodulin dependent cyclic AMP phosphodiesterase. This article envisages the various drugs being developed for treating MDR in cancer cells and especially the acridone derivatives which are being developed by the author.
Keywords: Acridones, calmodulin, multiple resistant protein (MRP), multidrug resistance (MDR), P-glycoprotein (P-gp)
Current Cancer Drug Targets
Title: Design of New Drug Molecules to be Used in Reversing Multidrug Resistance in Cancer Cells
Volume: 9 Issue: 3
Author(s): Y. c. Mayur, G. J. Peters, V. V.S. Rajendra Prasad, C. Lemos and N. K. Sathish
Affiliation:
Keywords: Acridones, calmodulin, multiple resistant protein (MRP), multidrug resistance (MDR), P-glycoprotein (P-gp)
Abstract: Over the past two decades, a number of chemical entities have been investigated in the continuing quest to reverse P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in cancer cells and some have undergone clinical trials, but currently none are in clinical use. Unfortunately, most of these agents suffer clinically from their intrinsic toxicity or from undesired effects on the pharmacokinetics of the accompanying anti-cancer drugs. An acridonecarboxamide (GF120918), Imidazo acridone (C1311) and timethylene acridone derivative 1,3-bis(9-oxoacridin-10-yl)-propane (PBA) have already been shown to be among the group of compounds known to modify P-gp mediated MDR in cancer. In the recent past it has been identified that various N10-substituted acridones can reverse the multidrug resistance (MDR) in cancer by selectively inhibiting the multidrug resistance associated protein (MRP) and calmodulin dependent cyclic AMP phosphodiesterase. This article envisages the various drugs being developed for treating MDR in cancer cells and especially the acridone derivatives which are being developed by the author.
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Mayur c. Y., Peters J. G., Rajendra Prasad V.S. V., Lemos C. and Sathish K. N., Design of New Drug Molecules to be Used in Reversing Multidrug Resistance in Cancer Cells, Current Cancer Drug Targets 2009; 9 (3) . https://dx.doi.org/10.2174/156800909788166619
DOI https://dx.doi.org/10.2174/156800909788166619 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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