Natural polymers as potential P-glycoprotein inhibitors: Pre-ADMET profile and computational analysis as a proof of concept to fight multidrug resistance in cancer
Kumaraswamy Gandla,
Fahadul Islam,
Mehrukh Zehravi,
Anandakumar Karunakaran,
Indu Sharma,
M. Akiful Haque,
Sanjay Kumar,
Kumar Pratyush,
Sachin A. Dhawale,
Firzan Nainu,
Sharuk L. Khan,
Md Rezaul Islam,
Kholoud Saad Al-Mugren,
Falak A. Siddiqui,
Talha Bin Emran,
Mayeen Uddin Khandaker
Affiliations
Kumaraswamy Gandla
Department of Pharmaceutical Analysis, Chaitanya (Deemed to be University), Himayath Nagar, Hyderabad 500075, Telangana, India
Fahadul Islam
Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
Mehrukh Zehravi
Department of Clinical Pharmacy Girls Section, Prince Sattam Bin Abdul Aziz University, Al-Kharj 11942, Saudi Arabia
Anandakumar Karunakaran
Department of Pharmaceutical Analysis, Vivekanandha Pharmacy College for Women, Beerachipalayam, Sankari West, Sankari, Salem, Tamil Nadu, - 637 303, India
Indu Sharma
Department of Physics, Career Point University, Hamirpur, Himachal Pradesh 176041, India
M. Akiful Haque
Department of Pharmaceutical Analysis, School of Pharmacy, Anurag University, Hyderabad, India
Sanjay Kumar
Department of Pharmacognosy, Laureate Institute of Pharmacy, VPO Kathog, Dehra, Kangra, Himachal Pradesh 176031, India
Kumar Pratyush
Department of Pharmaceutical Chemistry, Shri Vile Parle Kelavani Mandal's Institute of Pharmacy, Dhule, Maharashtra, 424001, India
Sachin A. Dhawale
Shreeyash Institute of Pharmaceutical Education and Research Aurangabad, 431 005, Maharashtra, India
Firzan Nainu
Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia
Sharuk L. Khan
Department of Pharmaceutical Chemistry, N.B.S. Institute of Pharmacy, Ausa 413520, Maharashtra, India; Department of Pharmaceutical Chemistry, School of Pharmacy, Anurag University, Hyderabad, India
Md Rezaul Islam
Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
Kholoud Saad Al-Mugren
Department of Physics, College of Science, Princess Nourah Bint Abdulrahman University, P.O. Box 84428 Riyadh 11671, Saudi Arabia; Corresponding author. Department of Physics, College of Science, Princess Nourah Bint Abdulrahman University, P.O. Box 84428 Riyadh 11671, Saudi Arabia
Falak A. Siddiqui
Department of Pharmaceutical Chemistry, N.B.S. Institute of Pharmacy, Ausa 413520, Maharashtra, India; Department of Pharmaceutical Chemistry, School of Pharmacy, Anurag University, Hyderabad, India; Corresponding author. Department of Pharmaceutical Chemistry, N.B.S. Institute of Pharmacy, Ausa 413520, Maharashtra, India
Talha Bin Emran
Department of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown University, Providence, RI 02912, USA; Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh; Corresponding author. Department of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown University, Providence, RI 02912, USA
Mayeen Uddin Khandaker
Centre for Applied Physics and Radiation Technologies, School of Engineering and Technology, Sunway University, Bandar Sunway 47500, Selangor, Malaysia
P-glycoprotein (P-gp) is known as the ''multidrug resistance protein'' because it contributes to tumor resistance to several different classes of anticancer drugs. The effectiveness of such polymers in treating cancer and delivering drugs has been shown in a wide range of in vitro and in vivo experiments. The primary objective of the present study was to investigate the inhibitory effects of several naturally occurring polymers on P-gp efflux, as it is known that P-gp inhibition can impede the elimination of medications. The objective of our study is to identify polymers that possess the potential to inhibit P-gp, a protein involved in drug resistance, with the aim of enhancing the effectiveness of anticancer drug formulations. The ADMET profile of all the selected polymers (Agarose, Alginate, Carrageenan, Cyclodextrin, Dextran, Hyaluronic acid, and Polysialic acid) has been studied, and binding affinities were investigated through a computational approach using the recently released crystal structure of P-gp with PDB ID: 7O9W. The advanced computational study was also done with the help of molecular dynamics simulation. The aim of the present study is to overcome MDR resulting from the activity of P-gp by using such polymers that can inhibit P-gp when used in formulations. The docking scores of native ligand, Agarose, Alginate, Carrageenan, Chitosan, Cyclodextrin, Dextran, Hyaluronic acid, and Polysialic acid were found to be −10.7, −8.5, −6.6, −8.7, −8.6, −24.5, −6.7, −8.3, and −7.9, respectively. It was observed that, Cyclodextrin possess multiple properties in drug delivery science and here also demonstrated excellent binding affinity. We propose that drug efflux-related MDR may be prevented by the use of Agarose, Carregeenan, Chitosan, Cyclodextrin, Hyaluronic acid, and/or Polysialic acid in the administration of anticancer drugs.
