Research Article | Volume: 8, Issue: 11, November, 2018

In silico analysis of plant phytochemicals against secreted aspartic proteinase enzyme of Candida albicans

S. S. Meenambiga R. Venkataraghavan R. Abhishek Biswal   

Open Access   

Published:  Nov 30, 2018

DOI: 10.7324/JAPS.2018.81120

Candida albicans, a polymorphic fungal species of human microflora, is pathogenic and known to cause immense damage to the host organism which includes biofilm formation, oral and skin infections in immune deficient individuals. Secreted aspartic proteinase (SAP) enzyme plays a major role in promoting virulence to C. albicans, and thus could be established as a drug target for Candida infections. As a result, inhibiting the enzyme’s active center using phytochemicals would reduce the severity of the enzyme’s virulence. The present work focuses on the in silico analysis of about 15 plant phytochemicals against the SAP enzyme using the AutoDock 4.2.6 software. The docking results were found to be promising with emodin having the highest binding score of −6.44 kCal/mol followed by the isoflavonoid equol with the binding score of −6.29 kCal/mol. Thus, these bioactive compounds could be used as leads for drugs targeting SAP enzymes in treating resistant Candida infections.

Keyword:     Candida albicans secreted aspartic proteinase (SAP) phytochemicals in silico AutoDock.


Meenambiga SS, Venkataraghavan R, Biswal A. In silico analysis of plant phytochemicals against secreted aspartic proteinase enzyme of Candida albicans. J App Pharm Sci, 2018; 8(11): 140–150.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Almagro JC, Beavers MP, Hernandez-Guzman F, Maier J, Shaulsky J, Butenhof K, Labute P, Thorsteinson N, Kelly K, Teplyakov A, Luo J. Antibody modeling assessment. Proteins Struct Funct Bioinf, 2011; 79:3050–66.

Alves LA, Freires ID, Pereira TM, Souza AD, Lima ED, Castro RD. Effect of Schinus terebinthifolius on Candida albicans growth kinetics, cell wall formation and micromorphology. Acta Odontol Scand, 2013; 71(3–4):965–71.

Aoki W, Kitahara N, Miura N, Morisaka H, Yamamoto Y, Kuroda K, Ueda M. Comprehensive characterization of secreted aspartic proteinases encoded by a virulence gene family in Candida albicans. J Biochem, 2011; 150:431–8.

Azevedo MM, Almeida CA, Chaves FC, Rodrigues IA, Bizzo HR, Alviano CS, Alviano DS. 7-hydroxycalamenene effects on secreted aspartic proteases activity and biofilm formation of Candida spp. Pharmacogn Mag, 2016; 12:36.

Barth G, Gaillardin C. Physiology and genetics of the dimorphic fungus Yarrowia lipolytica. FEMS Microbiol Rev, 1997; 19:219–37.

Benet LZ, Hosey CM, Ursu O, Oprea TI. BDDCS, the rule of 5 and drugability. Adv Drug Delivery Rev, 2016; 101:89–98.

Berman HM, Battistuz T, Bhat TN, Bluhm WF, Bourne PE, Burkhardt K, Feng Z, Gilliland GL, Iype L, Jain S, Fagan P. The protein data bank. Acta Cryst D, 2002; 58:899–907.

Borelli C, Ruge E, Lee JH, Schaller M, Vogelsang A, Monod M, Korting HC, Huber R, Maskos K. X-ray structures of Sap1 and Sap5: structural comparison of the secreted aspartic proteinases from Candida albicans. Proteins Struct Funct Bioinf, 2008; 72:1308–19.

Borg-von Zepelin M, Beggah S, Boggian K, Sanglard D, Monod M. The expression of the secreted aspartyl proteinases Sap4 to Sap6 from Candida albicans in murine macrophages. Mol Microbiol, 1998; 28(3):543–54.

Cadicamo CD, Mortier J, Wolber G, Hell M, Heinrich IE, Michel D, Semlin L, Berger U, Korting HC, Höltje HD, Koksch B. Design, synthesis, inhibition studies, and molecular modeling of pepstatin analogues addressing different secreted aspartic proteinases of Candida albicans. Biochem Pharmacol, 2013; 85:881–7.

Cao Y, Dai B, Wang Y, Huang S, Xu Y, Cao Y, Gao P, Zhu Z, Jiang Y. In vitro activity of baicalein against Candida albicans biofilms. Int J Antimicrob Agents, 2008; 32(1):73–7.

Carmona EM, Limper AH. Overview of treatment approaches for fungal infections. Clin Chest Med, 2017; 38:393–402.

Citoglu GS, Sever B, Antus SA, Baitz-Gacs E, Altanlar N. Antifungal flavonoids from Ballota glandulosissima. Pharm Biol, 2003; 41:483–6.

Corradi V, Mancini M, Santucci MA, Carlomagno T, Sanfelice D, Mori M, Vignaroli G, Falchi F, Manetti F, Radi M, Botta M. Computational techniques are valuable tools for the discovery of protein–protein interaction inhibitors: the 14-3-3σ case. Bioorg Med Chem Lett, 2011; 21:6867–71.

De Viragh PA, Sanglard D, Togni G, Falchetto R, Monod M. Cloning and sequencing of two Candida parapsilosis genes encoding acid proteinases. Microbiology, 1993; 139:335–42.

Gilfillan GD, Sullivan DJ, Haynes K, Parkinson T, Coleman DC, Gow NA. Candida dubliniensis: phylogeny and putative virulence factors. Microbiology, 1998; 144:829–38.

Janeczko M, MasÅ‚yk M, KubiÅ„ski K, Golczyk H. Emodin, a natural inhibitor of protein kinase CK2, suppresses growth, hyphal development, and biofilm formation of Candida albicans. Yeast, 2017; 34:253–65.

Keller NP, Turner G, Bennett JW. Fungal secondary metabolism—from biochemistry to genomics. Nat Rev Microbiol, 2005; 3:937–47.

Koelsch G, Tang J, Loy JA, Monod M, Jackson K, Foundling SI, Lin X. Enzymic characteristics of secreted aspartic proteinases of Candida albicans. Biochim Biophys Acta Protein Struct Mol Enzymol, 2000; 1480:117–31.

Korting HC, Patzak U, Schaller M, Maibach HI. A model of human cutaneous candidosis based on reconstructed human epidermis for the light and electron microscopic study of pathogenesis and treatment. J Infect, 1998; 36:259–67.

Lan CY, Rodarte G, Murillo LA, Jones T, Davis RW, Dungan J, Newport G, Agabian N. Regulatory networks affected by iron availability in Candida albicans. Mol Microbiol. 2004; 53(5):1451–69.

Lee H, Woo ER, Lee DG. Apigenin induces cell shrinkage in Candida albicans by membrane perturbation. FEMS Yeast Res, 2018; 18:foy003.

Lee JA, Chee HY. In vitro antifungal activity of equol against Candida albicans. Mycobiology, 2010; 38:328–30.

Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Delivery Rev, 2012; 64:4–17.

Luu TT, Malcolm N, Nadassy K. Pharmacophore modeling methods in focused library selection-applications in the context of a new classification scheme. Comb Chem High Throughput Screen, 2011; 14:488–99.

Martins CV, Da Silva DL, Neres AT, Magalhaes TF, Watanabe GA, Modolo LV, Sabino AA, De Fátima A, De Resende MA. Curcumin as a promising antifungal of clinical interest. J Antimicrob Chemother, 2008; 63:337–9.

Meenambiga SS, Rajagopal K. Antibiofilm activity and molecular docking studies of bioactive secondary metabolites from endophytic fungus Aspergillus nidulans on oral Camndida albicans. J App Pharm Sci, 2018; 8:37–45.

Meenambiga SS, Rajagopal K, Durga R. In silico docking studies on the components of Inonotus sp., a medicinal mushroom against cyclooxygenase-2 enzyme. Asian J Pharm Clin Res, 2015; 8:142–5.

Mishra S, Singh S, Misra K. Restraining pathogenicity in Candida albicans by taxifolin as an inhibitor of Ras1-pka pathway. Mycopathologia, 2017; 182:953–65.

Monod M, Togni G, Hube B, Sanglard D. Multiplicity of genes encoding secreted aspartic proteinases in Candida species. Mol Microbiol, 1994; 13:357–68.

Moore D, Robson GD, Trinci A. Biochemistry and developmental biology of fungi. In: 21st Century Guidebook to Fungi. Cambridge University Press, Cambridge, UK, pp 237–9, 2011.

Naglik JR, Challacombe SJ, Hube B. Candida albicans secreted aspartyl proteinases in virulence and pathogenesis. Microbiol Mol Biol Rev, 2003; 67:400–28.

Raut JS, Karuppayil SM. Phytochemicals as inhibitors of Candida biofilm. Curr Pharm Des, 2016; 22:4111–34.

Schaller M, Januschke E, Schackert C, Woerle B, Korting HC. Different isoforms of secreted aspartyl proteinases (Sap) are expressed by Candida albicans during oral and cutaneous candidosis in vivo. J Med Microbiol, 2001; 50:743–7.

Schaller M, Schackert C, Korting HC, Januschke E, Hube B. Invasion of Candida albicans correlates with expression of secreted aspartic proteinases during experimental infection of human epidermis. J Invest Dermatol, 2000; 114:712–7.

Schaller M, Thoma-Greber E, Korting HC, Hube B, Ollert MW, Schäfer W, Borg-von Zepelin M. In vivo expression and localization of Candida albicans secreted aspartyl proteinases during oral candidiasis in HIV-infected patients. J Invest Dermatol, 1999; 112(3):383–6.

Shahzad M, Sherry L, Rajendran R, Edwards CA, Combet E, Ramage G. Utilising polyphenols for the clinical management of Candida albicans biofilms. Int J Antimicrob Agents, 2014; 44(3):269–73.

Sutter J, Li J, Maynard A, Goupil A, Luu T, Nadassy K. New features that improve the pharmacophore tools from Accelrys. Curr Comput Aided Drug Des, 2011; 7:173–80.

Sydnor ER, Perl TM. Hospital epidemiology and infection control in acute-care settings. Clin Microbiol Rev, 2011; 24:141–73.

Teodoro GR, Brighenti FL, Delbem AC, Delbem ÁC, Khouri S, Gontijo AV, Pascoal AC, Salvador MJ, Koga-Ito CY. Antifungal activity of extracts and isolated compounds from Buchenavia tomentosa on Candida albicans and non-albicans. Future Microbiol, 2015a; 10:917–27.

Teodoro GR, Ellepola K, Seneviratne CJ, Koga-Ito CY. Potential use of phenolic acids as anti-Candida agents: a review. Front Microbiol, 2015b; 6:1420.

Tsang PW, Bandara HM, Fong WP. Purpurin suppresses Candida albicans biofilm formation and hyphal development. PLoS One, 2012; 7(11):e50866.

Xie C, Sun L, Meng L, Wang M, Xu J, Bartlam M, Guo Y. Sesquiterpenes from Carpesium macrocephalum inhibit Candida albicans biofilm formation and dimorphism. Bioorg Med Chem Lett, 2015; 25(22):5409–11.

Yordanov M, Dimitrova P, Patkar S, Saso L, Ivanovska N. Inhibition of Candida albicans extracellular enzyme activity by selected natural substances and their application in Candida infection. Can J Microbiol, 2008; 54:435–40.

Zhang Z, ElSohly HN, Jacob MR, Pasco DS, Walker LA, Clark AM. Natural products inhibiting Candida albicans secreted aspartic proteases from Lycopodium cernuum. J Nat Prod. 2002;65:979-85.

Zaugg C, Borg-von Zepelin M, Reichard U, Sanglard D, Monod M. Secreted aspartic proteinase family of Candida tropicalis. Infect Immun, 2001; 69:405–12

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