IN SILICO DOCKING STUDIES ON THE COMPONENTS OF INONOTUS SP., A MEDICINAL MUSHROOM AGAINST CYCLOOXYGENASE-2 ENZYME
Inonotus sp., mushroom is widely present and known for its medicinal property. This mushroom produces several bioactive compounds with various pharmaceutical uses. In the present study, about 8 biologically active compounds from Inonotus sp., were analyzed for its drug likeliness based on Lipinski's rule of five and inhibitor property against the COX-2 enzyme, a protein responsible for inflammation. The compounds which satisfy the Lipinski's rule namely inotilone, 4-(3,4-dihydroxyphenyl)butanone and hispidin were subjected to docking experiments using AutoDock 4.2. Molecular docking studies revealed that inotilone, hispidin and 4-(3,4-dihydroxyphenyl) buanone bind effectively to the active site region of COX-2 with a binding energy of -6.73, -7.78 and -5.63 respectively. Hence, compounds reported from Inonotus sp., were found to possess potential medicinal value with anti-inflammatory properties and this provides potential insight to develop new COX-2 inhibitors.
Inonotus sp., Inflammation, COX-2, AutoDock.
Moore D, Robson GD, Trinci A. Biochemistry and developmental biology of fungi. In: 21st Century Guidebook to Fungi. Cambridge: Cambridge University Press; 2011. p. 237-9.
Keller NP, Turner G, Bennett JW. Fungal secondary metabolism - from biochemistry to genomics. Nat Rev Microbiol 2005;3(12):937-47.
Cole R, Schweikert M. Handbook of Secondary Fungal Metabolites. Amsterdam: Elsevier; 2003. p. 1-3.
Kim YO, Park HW, Kim JH, Lee JY, Moon SH, Shin CS. Anti-cancer effect and structural characterization of endo-polysaccharide from cultivated mycelia of Inonotus obliquus. Life Sci 2006;79(1):72-80.
Rzymowska J. The effect of aqueous extracts from Inonotus obliquus on the mitotic index and enzyme activities. Boll Chim Farm 1998;137(1):13-5.
Song Y, Hui J, Kou W, Xin R, Jia F, Wang N, et al. Identification of Inonotus obliquus and analysis of antioxidation and antitumor activities of polysaccharides. Curr Microbiol 2008;57(5):454-62.
Kukulyanskaya TA, Kurchenko NV, Kurchenk VP, Babitskaya VG. Physicochemical properties of melanins produced by the sterile form of Inonotus obliquus (chagaâ€) in natural and cultivated fungus. Appl Biochem Microbiol 2002;38(1):58-61.
Mu H, Zhang A, Zhang W, Cui G, Wang S, Duan J. Antioxidative Properties of Crude Polysaccharides from Inonotus obliquus. Int J Mol Sci 2012;13(7):9194-206.
Wangun K, Vignie H. Isolation, Structure Elucidation and Evaluation of Anti-inflammatory and Anti-infectious Activities of Fungal Metabolites. Ph. D Dissertation, Council of Chemistry and Geo Science Faculty of the Friedrich-Schiller, University Jena; 2006.10. Lipsky LP, Abramson SB, Crofford L, Dubois RN, Simon LS, van de Putte LB. The classification of cyclooxygenase inhibitors. J Rheumatol 1998;25(12):2298-303.
Chajjed SS, Hiwani PB, Bastikar VA, Upasani CD, Udavant PB, Dhake AS, et al. Structure based design and in-silico molecular docking analysis of some novel benzamidazoles. Int J Chem Tech Res 2010;2:1135-140.
Sudha KN, Shakira M, Prasanthi P, Sarika N, Kumar ChN, Babu PA. Virtual screening for novel COX-2 inhibitors using the ZINC database. Bioinformation 2008;2(8):325-9.
Kitchen DB, Decornez H, Furr JR, Bajorath J. Docking and scoring in virtual screening for drug discovery: Methods and applications. Nat Rev Drug Discov 2004;3(11):935-49.
Kandasamy S, Sahu SK, Kandasamy K. In Silico studies on fungal metabolite against skin cancer protein (4, 5-Diarylisoxazole HSP90 Chaperone). ISRN Dermatol 2012;2012:626214.
Sharma R, Vijaya Kumar BS. In silico interaction studies on inhibitory action of endophytic fungal diketopiperazine and its related compounds on heat-shock protein 90 (hsp90). Asian J Biomed Pharm Sci 2014;4(28):25-9.
Mazurkiewicz W. Analysis of aqueous extract of Inonotus Obliquus. Pol Pharm Soc-Drug Res 2006;63(6):497-501.
Kurumbail RG, Stevens AM, Gierse JK, McDonald JJ, Stegeman RA, Pak JY, et al. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature 1996;384(6610):644-8.
Smith CJ, Morrow JD, Roberts LJ 2nd, Marnett LJ. Differentiation of monocytoid THP-1 cells with phorbol ester induces expression of prostaglandin endoperoxide synthase-1 (COX-1). Biochem Biophys Res Commun 1993;192(2):787-93.
Howe LR, Subbaramaiah K, Brown AM, Dannenberg AJ. Cyclooxygenase-2: A target for the prevention and treatment of breast cancer. Endocr Relat Cancer 2001;8(2):97-114.
Al Mofleh IA, Al Rashed RS. Nonsteroidal, antiinflammatory drug-induced gastrointestinal injuries and related adverse reactions: Epidemiology, pathogenesis and management. Saudi J Gastroenterol 2007;13(3):107-13.
Crabtree RH. A new type of hydrogen bond. J Sci 1998;282:2000-1.
Lee YG, Lee WM, Kim JY, Lee JY, Lee IK, Yun BS, et al. Src kinase-targeted anti-inflammatory activity of davallialactone from Inonotus xeranticus in lipopolysaccharide-activated RAW264.7 cells. Br J Pharmacol 2008;154(4):852-63.
Kuo YC. Effects of Inotilone on Inflammation and Inflammation Associated Tumorigenesis, Ph. D Dissertation, Graduate School-New Brunswick Rutgers, The State University of New Jersey, New Jersey; 2010.
Meenambiga SS, Rajagopal K. In silico studies on plant derived components of Cissus quadrangularis against COX-2 enzyme. Int J Pharm Pharm Sci 2014;6(8):483-7.
Virupakshaiah DB. Docking of Secondary metabolites derived from marine fungi with Hsp 90a protein in cancer treatment. J Adv Bioinform Appl Res 2014;5(2):92-6.
How to Cite
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.