STRUCTURE-BASED DOCKING STUDIES TOWARD EXPLORING THE POTENTIAL ANTICANCER ACTIVITY OF MORIN AGAINST NON-MELANOMA SKIN CANCER THERAPEUTIC DRUG TARGETS

Anjugam C; Sridevi M; Gnanendra Ts

doi:10.22159/ajpcr.2018.v11i4.23076

Authors

Anjugam C Department of Biochemistry, Vinayaka Missionâ€™s Kirupananda Variyar Medical College and Hospitals, Vinayaka Missions Research Foundation, Salem, Tamil Nadu, India.
Sridevi M Department of Biotechnology, Vinayaka Missionâ€™s Kirupananda Variyar Engineering College,Vinayaka Missions Research Foundation, Periyaseeragapadi, Salem, Tamil Nadu, India.
Gnanendra Ts Department of Biotechnology, Mahendra Arts and Science College (Autonomous), Kalippatti, Namakkal, Tamil Nadu, India.

DOI:

https://doi.org/10.22159/ajpcr.2018.v11i4.23076

Keywords:

Non-melanoma skin cancer, Cyclooxygenase-2, Peroxisome-proliferator-activated receptors, Molecular docking, Morin

Abstract

Â Objective: The purpose of this study is to explore the anticancer activity of morin compound against human cyclooxygenase-2 (COX-2) and peroxisome-proliferator-activated receptors (PPARs) isotypes (PPARÎ± and PPARÎ³) through in silico molecular docking studies.

Methods: The 3D structures of human COX-2 complexed with ibuprofen (PDB ID: 4PH9), PPARÎ± complexed with a synthetic agonist (2S)-2-(4- methoxy-3-{[(pyren-1-yl carbonyl) amino] methyl} benzyl) butanoic acid (PDB ID: 3VI8) and PPARÎ³ complexed indomethacin (PDB ID: 3ADX) were retrieved from protein databank. The cocrystallized sites were considered as binding sites, and the docking with morin compound was performed along with their respective cocrystals for each target and compared their interactions and binding affinities.

Results: It is observed that the morin compound exhibited better binding energy of -32.9528 kJ/mol against PPARÎ± followed by COX-2 (binding energy: âˆ’18.4311 kJ/mol) and PPARÎ³ (binding energy: âˆ’17.4228 kJ/mol) when compared to their cocrystallized ligands.

Conclusion: The present study suggests that morin compound might serve as potential alternatives in the prevention of skin cancers by showing better activity against PPARÎ±.

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References

Lanoy E. Epidemiology, risk factor and screening for melanoma and other skin cancers. Rev Prat 2014;64:31-6.

Bulliard JL, Panizzon RG, Levi F. Epidemiology of epithelial skin cancers. Rev Med Suisse 2009;5:882-4.

Fischer SM, Hawk ET, Lubet RA. Coxibs and other nonsteroidal anti-inflammatory drugs in animal models of cancer chemoprevention. Cancer Prev Res (Phila) 2011;4:1728-35.

Kripke ML. Antigenicity of murine skin tumors induced by ultraviolet light. J Natl Cancer Inst 1974;53:1333-6.

Rogers HW, Coldiron BM. Analysis of skin cancer treatment and costs in the United States Medicare population, 1996-2008. Dermatol Surg 2013;39:35-42.

Rogers HW, Weinstock MA, Harris AR. Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol 2010;146:283-7.

Elmets CA, Ledet JJ, Athar M. Cyclooxygenases: Mediators of UV-induced skin cancer and potential targets for prevention. J Invest Dermatol 2014;134:2497-502.

Shujiao L, Lilin H, Yong S. Cyclooxygenase-2 expression and association with skin cancer: A meta-analysis based on Chinese patients. J Can Res Ther 2016;12:288.

Khan AR, Sadiq IZ, Abdullahi LI, Danlami D, Taneja P. Chemoprotective role of bovine lactoferricin against 7, 12 dimethylbenz (a) anthracene induced skin cancer in female swiss albino mice. Int J Pharm Pharm Sci 2016;8:215-22.

Wilgus TA, Koki AT, Zweifel BS, Kusewitt DF, Rubal PA, Oberyszyn TM, et al. Inhibition of cutaneous ultraviolet light B-mediated inflammation and tumor formation with topical celecoxib treatment. Mol Carcinog 2003;38:49-58.

Seukeran DC, Newstead CG, Cunliffe WJ. The compliance of renal transplant recipients with advice about sun protection measures. Br J Dermatol 1998;138:311-4.

John R, Cesar L, Yhors C. The health benefits of natural skin UVA photoprotective compounds found in botanical sources. Int J Pharm Pharm Sci 2016;Sl:13-23.

Michalik L, Desvergne B, Wahli W. Peroxisome-proliferator-activated receptors and cancers: Complex stories. Nat Rev Cancer 2004;4:61-70.

He G, Muga S, Thuillier P, Lubet RA, Fischer SM. The effect of PPARgamma ligands on UV-or chemically-induced carcinogenesis in mouse skin. Mol Carcinog 2005;43:198-206.

Thuillier P, Anchiraico GJ, Nickel KP, Maldve RE, Gimenez-Conti I, Muga SJ, et al. Activators of peroxisome proliferator-activated receptor-alpha partially inhibit mouse skin tumor promotion. Mol Carcinog 2000;29:134-42.

Brecher AR. The role of cyclooxygenase-2 in the pathogenesis of skin cancer. J Drugs Dermatol 2002;1:44-7.

Meng H, Zhao F, Li T, Hongying C, Liuqing C, Weizhen W. Survivin and COX-2 expression in squamous cell skin cancer and basal cell skin Carcinoma. Chin J Dermato Venereol 2010;9:804-6.

Berman HM, Battistuz T, Bhat TN, Bluhm WF, Bourne PE, Burkhardt K, et al. The protein data bank. Acta Crystallogr D Biol Crystallogr 2002;58:899-907.

Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A, et al. PubChem substance and compound databases. Nucleic Acids Res 2016;44:D1202-13.

ACD/ChemSketch Freeware, version 12. Toronto, ON, Canada: Advanced Chemistry Development, Inc. Available from: http://www. acdlabs.com.

Weininger D. SMILES, a chemical language and information system. Introduction to methodology and encoding rules. J Chem Inf Comput Sci 1998;28:31-6.

Rarey M, Kramer B, Lengauer T, Klebe G. A fast flexible docking method using an incremental construction algorithm. J Mol Biol 1996;261:470-89.

Gnanendra S, Anusuya S, Natarajan J. Molecular modeling and active site analysis of SdiA homolog, a putative quorum sensor for Salmonella typhimurium pathogenecity reveals specific binding patterns of AHL transcriptional regulators. J Mol Model 2012;18:4709-19.

Stierand K, Maab P, Rarey M. Molecular complexes at a glance: Automated generation of two-dimensional complex diagrams. Bioinformatics 2006;22:1710-6.

Thompson SC, Jolley D, Marks R. Reduction of solar keratoses by regular sunscreen use. N Engl J Med 1993;329:1147-51.

Ibrahem NH. Extraction and characterization of Iraqi Artemisia dracunculus dried aerial parts extract though hplc and gc-ms analysis with evaluation of its antitumor activity against 7,12-dimethylbenze(a) anthracene induced skin cancer in mice. Int J Pharm Pharm Sci 2017;9:34-42.

Doucet-Personeni C, Bentley PD, Fletcher RJ, Kinkaid A, Kryger G, Pirard B, et al. A structure-based design approach to the development of novel, reversible AChE inhibitors. J Med Chem 2001;44:3203-15.

Duffy BC, Zhu L, Decornez H, Kitchen DB. Early phase drug discovery: Cheminformatics and computational techniques in identifying lead series. Bioorg Med Chem 2012;20:5324-42.

Durrant JD, Mccammon JA. Computer-aided drug-discovery techniques that account for receptor flexibility. Curr Opin Pharmacol 2010;10:770-4.