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Recent Patents on Anti-Cancer Drug Discovery

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ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

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Research Article

The Molecular Docking of Flavonoids Isolated from Daucus carota as a Dual Inhibitor of MDM2 and MDMX

Author(s): Ijaz Muhammad, Noor Rahman, Gul E. Nayab, Sadaf Niaz, Mohibullah Shah, Sahib G. Afridi, Haroon Khan*, Maria Daglia and Esra Capanoglu

Volume 15, Issue 2, 2020

Page: [154 - 164] Pages: 11

DOI: 10.2174/1574892815666200226112506

Price: $65

Abstract

Background: Cancer is characterized by overexpression of p53 associated proteins, which down-regulate P53 signaling pathway. In cancer therapy, p53 activity can be restored by inhibiting the interaction of MDMX (2N0W) and MDM2 (4JGR) proteins with P53 protein.

Objective: In the current, study in silico approaches were adapted to use a natural product as a source of cancer therapy.

Methods: In the current study in silico approaches were adapted to use a natural product as a source of cancer therapy. For in silico studies, Chemdraw and Molecular Operating Environment were used for structure drawing and molecular docking, respectively. Flavonoids isolated from D. carota were docked with cancerous proteins.

Result: Based on the docking score analysis, we found that compound 7 was the potent inhibitor of both cancerous proteins and can be used as a potent molecule for inhibition of 2N0W and 4JGR interaction with p53.

Conclusion: Thus the compound 7 can be used for the revival of p53 signaling pathway function however, intensive in vitro and in vivo experiments are required to prove the in silico analysis.

Keywords: Analysis, anticancer, Daucus carota, flavonoids, in silico, MDM2, MDMX, natural products.

« Previous Next »
[1]
Verma S, Grover S, Tyagi C, et al. Hydrophobic interactions are a key to MDM2 inhibition by polyphenols as revealed by molecular dynamics simulations and MM/PBSA free energy calculations. PLoS One 2016; 11(2): e0149014
[http://dx.doi.org/10.1371/journal.pone.0149014 ] [PMID: 26863418]
[2]
Muhseen ZT, Li G. Promising terpenes as natural antagonists of cancer: An in silico approach. Molecules 2019; 25(1): 155.
[http://dx.doi.org/10.3390/molecules25010155 ] [PMID: 31906032]
[3]
Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer 2013; 132(5): 1133-45.
[http://dx.doi.org/10.1002/ijc.27711] [PMID: 22752881]
[4]
Luzzati T, Parenti A, Rughi T. Economic growth and cancer incidence. Ecol Econ 2018; 146: 381-96.
[http://dx.doi.org/10.1016/j.ecolecon.2017.11.031]
[5]
Spector D. Optimizing cancer survivors’ health: The role of lifestyle behaviors. J Nurse Pract 2018; 14(4): 323-9.
[http://dx.doi.org/10.1016/j.nurpra.2017.12.007]
[6]
Schrag SJ, Wiener P. Emerging infectious disease: What are the relative roles of ecology and evolution? Trends Ecol Evol (Amst) 1995; 10(8): 319-24.
[http://dx.doi.org/10.1016/S0169-5347(00)89118-1 ] [PMID: 21237055]
[7]
Kubbutat MH, Ludwig RL, Levine AJ, Vousden KH. Analysis of the degradation function of Mdm2. Cell Growth Differ 1999; 10(2): 87-92.
[PMID: 10074902]
[8]
Tanikawa C, Zhang YZ, Yamamoto R, et al. The transcriptional landscape of p53 signalling pathway. EBioMedicine 2017; 20: 109-19.
[http://dx.doi.org/10.1016/j.ebiom.2017.05.017 ] [PMID: 28558959]
[9]
Wade M, Li YC, Wahl GM. MDM2, MDMX and p53 in oncogenesis and cancer therapy. Nat Rev Cancer 2013; 13(2): 83-96.
[http://dx.doi.org/10.1038/nrc3430 ] [PMID: 23303139]
[10]
Kwon SK, Saindane M, Baek KH. p53 stability is regulated by diverse deubiquitinating enzymes. Biochimica et Biophysica Acta (BBA)-. Rev Can 2017; 1868(2): 404-11.
[http://dx.doi.org/10.1016/j.bbcan.2017.08.001 ] [PMID: 28801249]
[11]
Liu Y, Deisenroth C, Zhang Y. RP–MDM2–p53 pathway: Linking ribosomal biogenesis and tumor surveillance. Trends Cancer 2016; 2(4): 191-204.
[http://dx.doi.org/10.1016/j.trecan.2016.03.002 ] [PMID: 28741571]
[12]
Laurie NA, Donovan SL, Shih CS, et al. Inactivation of the p53 pathway in retinoblastoma. Nature 2006; 444(7115): 61-6.
[http://dx.doi.org/10.1038/nature05194 ] [PMID: 17080083]
[13]
Moss SR, Turner SL, Trout RC, et al. Molecular epidemiology of Rabbit haemorrhagic disease virus. J Gen Virol 2002; 83(Pt 10): 2461-7.
[http://dx.doi.org/10.1099/0022-1317-83-10-2461 ] [PMID: 12237428]
[14]
Vassilev LT, Vu BT, Graves B, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004; 303(5659): 844-8.
[http://dx.doi.org/10.1126/science.1092472 ] [PMID: 14704432]
[15]
Leslie PL, Franklin DA, Liu Y, Zhang Y. p53 regulates the expression of LRP1 and apoptosis through a stress intensity-dependent MicroRNA feedback loop. Cell Rep 2018; 24(6): 1484-95.
[http://dx.doi.org/10.1016/j.celrep.2018.07.010 ] [PMID: 30089260]
[16]
Guy RK. Aryl-substituted imidazoles US9266860, 2016.
[17]
Dyer MA. Method for treating ocular cancer US8470785, 2013.
[18]
Chen G. mRNA-based gene expression for personalizing patient cancer therapy with an mdm2 antagonist WO2015000945, 2015.
[19]
Park M, Kim H. Anti-cancer mechanism of docosahexaenoic acid in pancreatic carcinogenesis: A mini-review. J Cancer Prev 2017; 22(1): 1-5.
[http://dx.doi.org/10.15430/JCP.2017.22.1.1 ] [PMID: 28382280]
[20]
Rauf A, Uddin G, Khan H, Raza M, Zafar M, Tokuda H. Anti-tumour-promoting and thermal-induced protein denaturation inhibitory activities of β-sitosterol and lupeol isolated from Diospyros lotus L. Nat Prod Res 2016; 30(10): 1205-7.
[http://dx.doi.org/10.1080/14786419.2015.1046381 ] [PMID: 26134930]
[21]
Khattak S, Khan H. Anti-cancer potential of phyto-alkaloids: A prospective review. Curr Cancer Ther Rev 2016; 12(1): 66-75.
[http://dx.doi.org/10.2174/1573394712666160617081638]
[22]
Al-Hrout A, Chaiboonchoe A, Khraiwesh B, et al. Safranal induces DNA double-strand breakage and ER-stress-mediated cell death in hepatocellular carcinoma cells. Sci Rep 2018; 8(1): 1-5.
[PMID: 29311619]
[23]
Ashktorab H, Soleimani A, Singh G, et al. Saffron: The golden spice with therapeutic properties on digestive diseases. Nutrients 2019; 11(5): 943.
[http://dx.doi.org/10.3390/nu11050943 ] [PMID: 31027364]
[24]
Al-Dabbagh B, Elhaty IA, Al Hrout A, et al. Antioxidant and anticancer activities of Trigonella foenum-graecum, Cassia acutifolia and Rhazya stricta. BMC Complement Altern Med 2018; 18(1): 240.
[http://dx.doi.org/10.1186/s12906-018-2285-7 ] [PMID: 30134897]
[25]
Hamza AA, Ahmed MM, Elwey HM, Amin A. Melissa officinalis protects against doxorubicin-induced cardiotoxicity in rats and potentiates its anticancer activity on MCF-7 cells. PLoS One 2016; 11(11): e0167049
[http://dx.doi.org/10.1371/journal.pone.0167049 ] [PMID: 27880817]
[26]
Amin A, Hamza AA, Daoud S, et al. Saffron-based crocin prevents early lesions of liver cancer: In vivo, in vitro and network analyses. Recent Patents Anticancer Drug Discov 2016; 11(1): 121-33.
[http://dx.doi.org/10.2174/1574892810666151102110248 ] [PMID: 26522014]
[27]
Amin S, Khan H. Revival of natural products: Utilization of modern technologies. Curr Bioact Compd 2016; 12: 103-6.
[http://dx.doi.org/10.2174/1573407212666160314195845]
[28]
Farooq U, Khan A, Naz S, et al. Sedative and antinociceptive activities of two new sesquiterpenes isolated from Ricinus communis. Chin J Nat Med 2018; 16(3): 225-30.
[http://dx.doi.org/10.1016/S1875-5364(18)30051-7 ] [PMID: 29576059]
[29]
Khan H, Amin S, Patel S. Targeting BDNF modulation by plant glycosides as a novel therapeutic strategy in the treatment of depression. Life Sci 2018; 196: 18-27.
[http://dx.doi.org/10.1016/j.lfs.2018.01.013 ] [PMID: 29341893]
[30]
Khan H. Marya, Amin S, Kamal MA, Patel S. Flavonoids as acetylcholinesterase inhibitors: Current therapeutic standing and future prospects. Biomed Pharmacother 2018; 101: 860-70.
[http://dx.doi.org/10.1016/j.biopha.2018.03.007 ] [PMID: 29635895]
[31]
Ortholand JY, Ganesan A. Natural products and combinatorial chemistry: back to the future. Curr Opin Chem Biol 2004; 8(3): 271-80.
[http://dx.doi.org/10.1016/j.cbpa.2004.04.011 ] [PMID: 15183325]
[32]
Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 2003; 3(10): 768-80.
[http://dx.doi.org/10.1038/nrc1189 ] [PMID: 14570043]
[33]
Liu RH. Potential synergy of phytochemicals in cancer prevention: Mechanism of action. J Nutr 2004; 134(12)(Suppl.): 3479S-85S.
[http://dx.doi.org/10.1093/jn/134.12.3479S ] [PMID: 15570057]
[34]
Hooft RW, Sander C, Vriend G. Objectively judging the quality of a protein structure from a Ramachandran plot. Comput Appl Biosci 1997; 13(4): 425-30.
[http://dx.doi.org/10.1093/bioinformatics/13.4.425 ] [PMID: 9283757]
[35]
Tomar NR, Singh V, Marla SS, Chandra R, Kumar R, Kumar A. Molecular docking studies with rabies virus glycoprotein to design viral therapeutics. Indian J Pharm Sci 2010; 72(4): 486-90.
[http://dx.doi.org/10.4103/0250-474X.73905 ] [PMID: 21218060]
[36]
Bandaru S, Ponnala D, Lakkaraju C, Bhukya CK, Shaheen U, Nayarisseri A. Identification of high affinity non-peptidic small molecule inhibitors of MDM2-p53 interactions through structure-based virtual screening strategies. Asian Pac J Cancer Prev 2015; 16(9): 3759-65.
[http://dx.doi.org/10.7314/APJCP.2015.16.9.3759 ] [PMID: 25987034]
[37]
López-Lázaro M. Distribution and biological activities of the flavonoid luteolin. Mini Rev Med Chem 2009; 9(1): 31-59.
[http://dx.doi.org/10.2174/138955709787001712 ] [PMID: 19149659]
[38]
Seelinger G, Merfort I, Wölfle U, Schempp CM. Anti-carcinogenic effects of the flavonoid luteolin. Molecules 2008; 13(10): 2628-51.
[http://dx.doi.org/10.3390/molecules13102628 ] [PMID: 18946424]
[39]
Kang KP, Park SK, Kim DH, et al. Luteolin ameliorates cisplatin-induced acute kidney injury in mice by regulation of p53-dependent renal tubular apoptosis. Nephrol Dial Transplant 2011; 26(3): 814-22.
[http://dx.doi.org/10.1093/ndt/gfq528 ] [PMID: 20817674]
[40]
Shangary S, Qin D, McEachern D, et al. Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition. Proc Natl Acad Sci USA 2008; 105(10): 3933-8.
[http://dx.doi.org/10.1073/pnas.0708917105 ] [PMID: 18316739]

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