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Reversal of multidrug resistance and antitumor promoting activity of 3-oxo-6β-hydroxy- β-amyrin isolated from Pistacia integerrima

ABDUR RAUF1,*, SAUD BAWAZEER2,*, MUSLIM RAZA3, EMAN EL-SHARKAWY4, MD. HABIBUR RAHMAN5,6, MOHAMED A. EL-ESAWI7, GHIAS UDDIN8, BINA S. SIDDIQUI9, ANEES AHMED KHALIL10, JOSEPH MOLNAR11, AKOS CSONKA11, DIÁNA SZABÓ12, HAROON KHAN13, MOHAMMAD S. MUBARAK14, TAIBI BEN HADDA15, MUDYAWATI KAMARUDDIN16, SEEMA PATEL17

1 Department of Chemistry, University of Swabi, Anbar, 23561, Khyber Pakhtunkhwa Pakistan
2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 24211, Saudi Arabia
3 State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, 100029, China
4 Chemical Departments, Faculty of Science, Northern Borders University, Arar, 91431, Saudi Arabia
5 Department of Pharmacy, Southeast University, Banani-1213, Dhaka, Bangladesh
6 Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Seoul, South Korea
7 Botany Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt
8 Institute of Chemical Sciences, University of Peshawar, Peshawar, 25120, Pakistan
9 H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
10 University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore, 54000, Pakistan
11 Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, 6700, Hungary
12 Department of Oto-Rhino-Laryngology and Head-Neck Surgery, Faculty of Medicine, University of Szeged, Szeged, 6700, Hungary
13 Department of Pharmacy, Abdul Wali Khan University, Mardan, 23200, Pakistan
14 Department of Chemistry, The University of Jordan, Amman, 11942, Jordan
15 LCM Laboratory, Faculty of Sciences, Mohamed First University, Oujda, 60000, Morocco
16 Institution of Health Science of Tahirah Al Baeti Bulukumba, South Sulawesi, 92352, Indonesia
17 Bioinformatics and Medical Informatics Research Center, San Diego State University, San Diego, 92182, USA

* Address correspondence to: Abdur Rauf, email; Saud Bawazeer, email

BIOCELL 2021, 45(1), 139-147. https://doi.org/10.32604/biocell.2021.013277

Abstract

The bioactive triterpenoid 3-oxo-6-β-hydroxy-β-amyrin (1) has been isolated from multiple plant sources. In this study, chloroform fraction of Pistacia integerrima extract was processed for the isolation of the compound. The compound identity was confirmed by advanced spectroscopy technique. X-ray crystallography was applied for molecular structure confirmation. In addition, compound 1 was screen for its activity on reversal of MDR (multidrug resistance) mediated by P-gp (P-glycoprotein). This was accomplished by using rhodamine123 exclusion on multidrug-resistant human ABCB1 gene transfected mouse T-lymphoma cell line. Outcomes revealed that MDR reversing effect was comparable to verapamil as positive control in vitro. Treatment of TPA-induced tumor promotion with 3-oxo-6β-hydroxy- β-amyrin led to reduction in the applied anti-tumor promotion experiment. The chemo-preventive effect of 3-oxo-6β-hydroxy- β- amyrin was comparable to curcumin as positive control based on the reduction of immediate early tumor antigen expression. Molecular docking by applying Autodock Vina 1 and i-GEMDOCK v 2.1 tools indicated that compound 1 gives good docking results, as determined by their fitness score and specificity. Moreover, results showed that compound 1 isolated from Pistacia integerrima precisely attached to a region where co-crystallized ligand for receptor previously existed. Our findings may explain the use of Pistacia integerrima plant extracts as an anticancer agent in folk medicine.

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RAUF, A., BAWAZEER, S., RAZA, M., EL-SHARKAWY, E., RAHMAN, M. H. et al. (2021). Reversal of multidrug resistance and antitumor promoting activity of 3-oxo-6β-hydroxy- β-amyrin isolated from Pistacia integerrima. BIOCELL, 45(1), 139–147.

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