Background: Multi Drug Resistance (MDR) is one of the main hindrances in
the successful treatment of cancer by natural agents. Most of the natural anticancer drugs
are effluxed by the P-glycoprotein resulting in the failure of cancer chemotherapy. Phenothiazines
and related drugs are one of the first drugs investigated for the reversal of
MDR. Exhaustive studies have been done to develop potent phenothiazines analogues for
MDR reversal activity.
Materials and Methods: Quantitative Structural Activity Relationship (QSAR) and
Structural Activity Relationship (SAR) studies of phenothiazines have provided some
fruitful results in order to develop potent anti-MDR phenothiazine drugs but no success
has been achieved yet. The main mechanism through which phenothiazines act on the Pglycoprotein
includes the same binding site of vinblastine drug and it inhibits the efflux
of such drugs. To develop a potent anti-MDR agent, it is indispensable to study the
mechanism of efflux of anticancer drugs by P-gp, SAR and QSAR studies of phenothiazines
as anti-MDR agents and mechanism of phenothiazines as anti-MDR agents simultaneously.
Conclusion: This review will discuss the work done on the SAR and QSAR of phenothiazines
as anti-MDR agents along with their putative mechanism of action as MDR reversal
Keywords: Phenothiazines, p-glycoprotein, MDR, cancer chemotherapy, anti cancer, SAR.
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