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Phenothiazines and Related Drugs as Multi Drug Resistance Reversal Agents in Cancer Chemotherapy Mediated by p-glycoprotein

[ Vol. 13 , Issue. 1 ]

Author(s):

Ravinesh Mishra*, Swati Sareen, Bhartendu Sharma, Shubham Goyal, Gurpreet Kaur, Sweta Bhardwaj, Anees A. Siddiqui, Asif Husain, Rajeev K. Singla, Mohd Rashid, Deepak Kumar, Bhawana Sati, Nishtha Shalmali and Rajiv Kumar   Pages 28 - 42 ( 15 )

Abstract:


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 agents.

Keywords:

Phenothiazines, p-glycoprotein, MDR, cancer chemotherapy, anti cancer, SAR.

Affiliation:

School of Pharmacy and Emerging Sciences, Baddi University of Emerging Sciences and Technology, Baddi (Solan), Himachal Pradesh 163205, School of Pharmacy and Emerging Sciences, Baddi University of Emerging Sciences and Technology, Baddi (Solan), Himachal Pradesh 163205, School of Pharmacy and Emerging Sciences, Baddi University of Emerging Sciences and Technology, Baddi (Solan), Himachal Pradesh 163205, School of Pharmacy and Emerging Sciences, Baddi University of Emerging Sciences and Technology, Baddi (Solan), Himachal Pradesh 163205, School of Pharmacy and Emerging Sciences, Baddi University of Emerging Sciences and Technology, Baddi (Solan), Himachal Pradesh 163205, Department of Pharmaceutical Chemistry, University School of Sciences, Rayat Bahra University, Mohali, Punjab 140104, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, Netaji Subhas Institute of Technology (Affiliated to University of Delhi), Dwarka, New Delhi 110078, Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy and Dentistry, Buraydah Colleges, Buraydah, Al-Qassim 31717, Department of Pharmaceutical Chemistry, School of Pharmacy, Sharda University, Greater Noida, Uttar Pradesh 201306, Department of Pharmacy, Banasthali Vidyapeeth, Tonk, Rajasthan 304001, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, Centre for Medicinal Chemistry, Delhi Pharmaceutical Sciences and Research University, New Delhi 110017

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