P-Glycoprotein Mediated Multidrug Resistance Reversal by Phytochemicals: A Review of SAR & Future Perspective for Drug Design

Author(s): Safiulla Basha Syed, Mohane Selvaraj Coumar

Journal Name: Current Topics in Medicinal Chemistry

Volume 16 , Issue 22 , 2016

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Graphical Abstract:


A major impediment for cancer chemotherapy is the development of multidrug-resistance (MDR). Continuous use of chemotherapeutic drugs during cancer therapy induces the expression of PGlycoprotein (P-gp, MDR1), an ATP dependant transporter, which in turn reduces the intracellular accumulation of chemotherapeutic drugs leading to MDR. Extensive research over the years has identified several potential P-gp inhibitors, both synthetic as well as natural origin, to overcome the MDR during cancer chemotherapy. In this review, we discuss the cellular pathways involved and transcription factors regulating the expression of P-gp. A number of phytochemicals are reported to inhibit P-gp activity and MDR1 expression; the structure-activity relationship (SAR) among the phytochemicals for P-gp inhibition and the effect of these phytochemicals on cellular signaling pathways regulating P-gp expression are discussed in detail. Moreover, structural biology and mutagenesis studies on P-gp along with docking studies throw light on the structural requirements for P-gp inhibition. Insight provided in the review about the phytochemicals molecular mechanism and SAR could catalyze the design of potent P-gp inhibitors in the future and could help to overcome MDR in cancer chemotherapy.

Keywords: Chemotherapy, Multidrug resistance (MDR), P-glycoprotein (P-gp), Phytochemicals, Structure Activity Relationship.

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Article Details

Year: 2016
Published on: 29 June, 2016
Page: [2484 - 2508]
Pages: 25
DOI: 10.2174/1568026616666160212123814
Price: $65

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