title: P-Glycoprotein Mediated Multidrug Resistance Reversal by Phytochemicals: A Review of SAR & Future Perspective for Drug Design.
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.
authors.forename: Safiulla Basha
authors.initials: SB
authors.lastname: Syed
authors.affiliation: Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Kalapet, Pondicherry 605014, India. mohane@bicpu.edu.in.
authors.forename: Mohane Selvaraj
authors.initials: MS
authors.lastname: Coumar
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D015195:Drug Design; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D064209:Phytochemicals / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D064209:Phytochemicals