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In Silico Docking, Enzyme Inhibition Assay of the Bioactive Compounds Isolated from Fusarium oxysporum

Research Paper | February 1, 2020

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Faheem Ullah, Bashir Ahmad, Shumaila Rauf, Abid Ali Khan

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Int. J. Biosci.16( 2), 421-435, February 2020

DOI: http://dx.doi.org/10.12692/ijb/16.2.421-435


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Two naphthoquinones; 8-O-methylbostrycoidin (1) and 9-O-methylanhydrofusarubin (2) were purified from the ethyl acetate fraction of the crude from Fusarium oxysporum and characterized through spectrometric techniques.  These metabolites were tested against phosphodiesterase-I, urease and carbonic anhydrase-II.  Both the naphthoquinones displayed substantial inhibition of phosphodiesterase-1 with IC50 value of 65 ± 3.01 and 30.10 ± 2.12 µM, respectively when compared with the standard EDTA (IC50 = 24 ± 0.22). Similarly, both the compounds showed significant activity against urease with IC50 values equal to 45 ± 1.45 and 67 ± 6.23 µM, respectively, while thiourea was used as standard for urease inhibition assay with IC50 value of 21 ± 0.12 µM. Most significant activity was observed against carbonic anhydrase-II for both of the compounds (86.31% and 73.80% inhibition, respectively) as compared to the standard acetazolamide (89.44%). Absorption, distribution, metabolism and excretion (ADME) properties of both compounds were calculated using SwissADME server, and showed considerable scores of drug properties. Molecular docking studies were performed for both the compounds using PatchDock server.  It was observed that the binding affinities of compound (1) are -101.64, -117.32 and -93.19 kcal/mol (atomic contact energy (ACE) of Patchdock) with PDE, urease and carbonic anhydrase, respectively and stands comparatively better than the standards; i.e., -80.77 (EDTA), -69.61 (thiourea) and -49.25 kcal/mol (Acetazolamide). Similarly, the binding affinities of compound (2) are higher with the receptor proteins (-87.76, -86.20 and -92.12 kcal/mol with PDE, urease and carbonic anhydrase, respectively) than the standard inhibitors (-80.77 (EDTA), -69.61 (thiourea) and -49.25 kcal/mol (Acetazolamide).


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In Silico Docking, Enzyme Inhibition Assay of the Bioactive Compounds Isolated from Fusarium oxysporum

Arabski M, Konieczna I, Sołowiej D, Rogoń A, Kolesińska B, Kamiński Z, Kaca W. 2010. Are anti-Helicobacter pylori urease antibodies involved in atherosclerotic diseases? Clinical biochemistry 43(1-2), 115-123. https://doi.org/10.1016/j.clinbiochem.2009.09.0.16

Biovia DS, Biovia Workbook Release. 2017. BIOVIA Pipeline Pilot, Release 2017, San Diego: Dassault Systèmes.

Cheminformatics M. 2015. Web-enabled software for large-scale calculation of molecular properties and database searches. Free online molecular descriptor calculations.

Daina A, Michielin O, Zoete V. 2017. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific reports 7, 42717. https://doi.org/10.1038/srep42717

Deng CM, Liu SX, Huang CH, Pang JY, Lin YC. (2013). Secondary metabolites of a mangrove endophytic fungus Aspergillus terreus (No. GX7-3B) from the South China Sea. Marine drugs 11(7), 2616-2624. https://doi.org/10.3390/md11072616

Dunn BE, Phadni SH. 1998. Structure, function and localization of Helicobacter pylori urease. The Yale journal of biology and medicine 71(2), 63.

Follmer C. 2010. Ureases as a target for the treatment of gastric and urinary infections. Journal of clinical pathology 63(5), 424-430.

Kakiuchi S, Yamazaki R, Teshima Y, Uenishi K, Miyamoto E. 1975. Multiple cyclic nucleotide phosphodiesterase activities from rat tissues and occurrence of a calcium-plus-magnesium-ion-dependent phosphodiesterase and its protein activator. Biochemical Journal 146(1), 109-120. https://doi.org/10.1042/bj14601.09

Khan AA, Bacha N, Ahmad B, Bakht J, Lutfullah G, Ali J. 2017. Synthesis of secondary metabolites by Cladosporium resinae (NRL-6437) under different growth media and chemical inducers and their pharmaceutical activity. Pakistan journal of pharmaceutical sciences 30(5), 1617-1624.

Khan AA, Bashir A, Lutfullah G, Hussain Z, Bacha N. 2013. Biological Screening of the crude extract isolated from a soil born fungi Cladosporium carrionii. Pakistan Journal of Weed Science Research 19(4).

Konieczna I, Kwinkowski M, Kolesinska B, Kaminski Z, Zarnowiec P, Kaca W. 2012. Detection of antibodies against synthetic peptides mimicking ureases fragments in sera of rheumatoid arthritis patients. Protein and peptide letters 19(11), 1149-1154. https://doi.org/10.2174/092986612803217.123

Li Q, Csetenyi L, Gadd GM. 2014. Biomineralization of metal carbonates by Neurospora crassa. Environmental science & technology 48(24), 14409-14416.

Luo J, Yan Zy, Guo XH, WANG Yl. 2007. Isolation, identification and the antibacterial activity of endophytic fungi in Euphorbia nematocypha Hand.-Mazz. West China Journal of Pharmaceutical Sciences 22(4), 380.

Mills N. 2006. ChemDraw Ultra 10.0 CambridgeSoft, 100 CambridgePark Drive, Cambridge, MA 02140. www. cambridgesoft. com. Commercial Price: 1910fordownload, 2150 for CD-ROM; Academic Price: 710fordownload, 800 for CD-ROM: ACS Publications. https://doi.org/10.1021/ja06978.75

Perry MJ, Higgs GA. 1998. Chemotherapeutic potential of phosphodiesterase inhibitors. Current opinion in chemical biology 2(4), 472-481. https://doi.org/10.1016/S1367-5931(98)801.23-3

Pretsch A, Nagl M, Schwendinger K, Kreiseder B, Wiederstein M, Pretsch D, Genov M, Hollaus R, Zinssmeister D, Debbab A. 2014. Antimicrobial and anti-inflammatory activities of endophytic fungi Talaromyces wortmannii extracts against acne-inducing bacteria. PLOS ONE, 9(6), e97929.

Schneidman-Duhovny D, Inbar Y, Nussinov R, Wolfson HJ. 2005. PatchDock and SymmDock: servers for rigid and symmetric docking. Nucleic acids research 33(2), W363-W367. https://doi.org/10.1093/nar/gki4.81

Schüttelkopf AW, Van Aalten DM. 2004. PRODRG: a tool for high-throughput crystallography of protein–ligand complexes. Acta Crystallographica Section D: Biological Crystallography 60(8), 1355-1363. https://doi.org/10.1107/S0907444904011679

Şentürk M, Gülçin İ, Beydemir Ş, Küfrevioğlu Öİ, Supuran CT. 2011. In vitro inhibition of human carbonic anhydrase I and II isozymes with natural phenolic compounds. Chemical biology & drug design 77(6), 494-499.

Sippl MJ. 1993. Recognition of errors in three‐dimensional structures of proteins. Proteins: Structure, Function, and Bioinformatics 17(4), 355-362.

Strobel G, Ford E, Worapong J, Harper JK, Arif AM, Grant DM, Fung PC, Chau RMW. 2002. Isopestacin, an isobenzofuranone from Pestalotiopsis microspora, possessing antifungal and antioxidant activities. Phytochemistry 60(2), 179-183. https://doi.org/10.1016/S0031-9422(02)000.62-6

Tatum J, Baker R, Berry R. 1985. Naphthoquinones produced by Fusarium oxysporum isolated from citrus. Phytochemistry 24(3), 457-459.

Vardanyan R, Hruby V. 2016. Synthesis of best-seller drugs: Academic press.

Weber D, Sterner O, Anke T, Gorzalczancy S, Martino V, Acevedo C. 2004. Phomol, a new antiinflammatory metabolite from an endophyte of the medicinal plant Erythrina crista-galli. The Journal of Antibiotics 57(9), 559-563.

Wiederstein M, Sippl MJ. 2007. ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic acids research 35(2), W407-W410. https://doi.org/10.1093/nar/gkm2.90

Willard L, Ranjan A, Zhang H, Monzavi H, Boyko RF, Sykes BD, Wishart DS. 2003. VADAR: a web server for quantitative evaluation of protein structure quality. Nucleic acids research, 31(13), 3316-3319.

Xu D, Zhang Y. 2011. Improving the physical realism and structural accuracy of protein models by a two-step atomic-level energy minimization. Biophysical journal 101(10), 2525-2534. https://doi.org/10.1016/j.bpj.2011.10.0.24

Zhang Z, Li Y, Lin B, Schroeder M, Huang B. 2011. Identification of cavities on protein surface using multiple computational approaches for drug binding site prediction. Bioinformatics 27(15), 2083-2088. http://dx.doi.org/10.1093/bioinformatics/btr331