In silico prediction and molecular docking study on the interaction of bioactive compounds of Adenanthera pavonina exploring the potential antifungal activity against Candida glabrata cell wall proteins
Abstract
Candida glabrata infections being resistant to many azole antifungal agents, are difficult to treat. Various parts of Adenanthera pavonina have been used in traditional medicine. In the present study, an attempt was made to screen the bioefficacy of the identified phytoconstituents of A. pavonina on an in silico platform and identify some potential drug-like molecules that can impede important drug targets of C. glabrata using the molecular docking method. In a previous study related to the current research, the phytochemical profiling of the methanolic stem extract of A. pavonina was carried out using GC-MS to identify the phytoconstituents. The three-dimensional structure of the fungal receptors were derived by homology modeling using Modeller9v7 and the same for the ligands for which the structures were not available were drawn by ACD chemSketch. The docking of ligands and receptors were performed using PatchDock software. Druglikeliness and pharmacodynamics properties were evaluated using SWISS-ADME. GC-MS analysis of the A. pavonina extract revealed the presence of 17 phyto compounds, of which 2 heptyl 1,3dioxolane and methyl 4-o-methyl-d-arabinopyranoside best docked with the epithelial adhesion protein 6 receptor and cell wall transcription factor ACE2. Methyl 4-o-methyl-d-arabinopyranoside also best docked with the integral cell wall protein receptor. Although other compounds have shown good scores related to docking 2 heptyl 1, 3 dioxolane had an excellent binding affinity than the other ligands thus signifying its potent antifungal activity. 2 Heptyl 1, 3 Dioxolane was found to be BBB positive and 4-O-Methyl-D-arabinopyranoside is BBB negative. As the finding indicates, the two phyto compounds present in the methanolic stem extract of A. pavonina demonstrated good docking scores when docked with specific fungal cell wall receptors and thus can prove to be appropriated for the lead molecule.
Keywords:
Candida glabrata, Adenanthera pavonina, molecular docking, antifungal activity, 2 heptyl 1, 3 dioxolaneDOI
https://doi.org/10.25004/IJPSDR.2021.130108References
Parivuguna V, Gnanaprabhal R, Dhanabalan R, Doss A. Antimicrobial properties and phytochemical constituents of Rheo discolor Hance. Ethnobot Leaflets. 2008; 12: 841-45.
Davis J. Inactivation of the antibiotics and the dissemination of resistance genes. Science. 1994; 264: 375-382.
Ng PC. Systemic fungal infections in neonates. Arch Dis of Childhood. 1994; 71: F130–F135.
Service RF. Antibiotics that resist resistance. Science. 1995 ; 270: 724-727.
Gonzalez CE, Venzon D, Lee S, Mueller BU, Pizzo PA, Walsh TJ. Risk factors for fungemia in children infected with human immunodeficiency virus: a case-control study. Clin Infect Dis. 1996; 23: 515–521.
Sinnott, J. T. (1987). Candida (Torulopsis) glabrata. Infect. Control. 8:334–336.
Sobel, JD. Pathogenesis and epidemiology of vulvovaginal candidiasis. Ann. N.Y. Acad. Sci. 1988. 544: 547–557.
Hitchcock CA, Pye GW, Troke PF, Johnson EM, Warnock DW. Fluconazole resistance in Candida glabrata. Antimicro. Agents Chemo. 1993; 37: 1962–1965.
Parekh J, Chanda S. In vitro antimicrobial activities of extracts of Launaea procumbens Roxb. (Labiateae), Vitis vinifera L. (Vitaceae) and Cyperes rotundus L. (Cyperaceae). Afri J Biomed Res. 2006; 9: 89-93.
Watt JM, Breyer-Brandwijk MG. The medicinal and poisonous plants of southern and eastern Africa. 2nd Edn. E and S Livingstone Ltd. Edinburgh.1962.
Holdsworth DK. Medicinal Plants of Papua New Guinea, South Pacific Commission Technical paper No.175, Noumea, New Caledonia. 1977.
Kirtikar KR, Basu BD. Indian Medicinal Plants. Bishen Singh, Mahandra Pal Singh Publishers, Dehradun, India. 1980; 1: 802-803.
Burkill HM. The useful plants of West Tropical Africa. Royal Botanical Gardens, Kew, Richmond, United Kingdom. 1994; Vol. 2.
Jayasinghe PKIDE, Bandara BMR., Ekanayaka EWMA, Thevanesam V. Screening for antimicrobial activity of Acronychia pedunculata (Ankenda) and Adenanthera pavonina (Madatiya) against bacteria causing skin and wound infections in humans. Proceedings of the Peradeniya University Research Sessions, Sri Lanka. 2006; 11: 105.
Duke JA. Dr. Duke's Phytochemical and Ethnobotanical Databases. Green Pharmacy Garden, Fulton. 2009.
Olajide OA, Echianu CA, Adedapo AD, Makinde JM. Anti-inflammatory studies on Adenanthera pavonina seed extract. Inflammopharmacology. 2004; 12(2): 196-202.
Adedapo ADA, Osude YO, Adedapo AA, Moody JO, Adeagbo AS, Olumayokun A, Olajide OA, Makinde JM. Blood pressure lowering effect of Adenanthera pavonina seed extract on normotensive rats. Rec Nat Prod. 2009; 32: 82-89.
Rodrigo SK, Jayasinghe ULB, Bandara BMR. Antifungal, antioxidant and cytotoxic activity of Acronychia pedunculata and Adenanthera pavonina. Proceedings of the Peradeniya University Research Sessions, Sri Lanka. 2007; 12(1): 94-95.
Bhadran S, George SA, Malla, S and Harini BP. Screening of bioprotective properties of various plant extracts and gas chromatography-mass spectrometry profiling of Adenanthera pavonina stem extract. Asian J Pharm Clin Res. 2017; 10: 188-94.
Blaney J, Dixon J. A good ligand is hard to find: Automated docking methods, Perspect. Drug Disc. Des. 1993; 1: 301-319.
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): 935-949.
Huang SY, Zou X. An iterative knowledge-based scoring function to predict protein-ligand interactions: I. Derivation of interaction potentials. J. Comput. Chem., 2006; 27: 1866–1875.
Srivastava V, Gupta SP, Siddiqi MI, Mishra BN. Molecular docking studies on quinazoline antifolate derivatives as human thymidylate synthase inhibitors, Bioinform. 2010; 4: 357-365.
Fukunishi Y, Nakamura H. Prediction of ligand-binding sites of proteins by molecular docking calculation for a random ligand library. Protein Sci. 2011; 20: 95–106.
Ehrlich LP, Wadey RC. Protein-protein docking. Reviews in Computational Chemistry. 2003; 17: 61.
Chen R, Mintseris J, Janin J, Weng Z. A protein–protein docking benchmark. Proteins. 2003; 52: 88–91.
Smith RD, Engdahl AL, Dunbar JB Jr, Carlson HA. 2012. Biophysical limits of protein-ligand binding. J Chem Inf Model., 52(8): 2098-106.
Gardiner EJ, Willett P, Artymiuk PJ. Protein docking using a genetic algorithm. Proteins. 2001; 44: 44–56.
Gray JJ, Moughon S, Wang C, Schueler-Furman O, Kuhlman B, Rohl CA, Baker D. Protein–protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations. J Mol Biol. 2003; 331: 281–299.
Duhovny D, Nussinov R, Wolfson HJ. Efficient unbound docking of rigid molecules. In: Guigo R., Gusfield D., editors. Proceedings of the Fourth International Workshop on Algorithms in Bioinformatics. Springer-Verlag GmbH Rome, Italy. 2002; 185–200.
Pagenkopf B. ACD/HNMR Predictor and ACD/CNMR Predictor advanced chemistry development. J Am Chem Soc. 2005; 127 (9): 3232–3232.
Mani P, Menakha M, Al- Aboody MS, Alturaiki W, Vijayakumar R. Molecular docking of bioactive compounds from Piper plants against secreted aspartyl proteinase of Candida albicans causing oral candidiasis. International Journal of Pharmaceutical and Clinical Research, 2016; 8(10): 1380-1389.
Daina, A., Michielin, O. & Zoete, V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017; 7: 42717.
Antoine Daina , Vincent Zoete. A BOILED‐Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules. ChemMedChem 2016; 11(11):1117-1121.
Lengauer T, Rarey M. Computational methods for biomolecular docking. Curr Opin Struc Bio. 1996; 6 (3): 402–406.
Dar AM, Mir S. Molecular Docking: Approaches, types, applications and basic challenges. J Anal Bioanal Tech. 2017; 8: 356.
McPhillie MJ, Cain RM, Narramore S, Fishwick CW, Simmons KJ. Computational methods to identify new antibacterial targets. Chem Biol Drug Des. 2015; 85: 22–29.
Pasko MT, Piscitelli SC, Van Slooten AD. Fluconazole: A New Triazole Antifungal Agent. DICP. 1990; 24(9): 860–867.
Latha R, Fathima M, Ganesan S. GC-MS analysis and in silico docking analysis of extracts of Acacia torta Craib. Asi J Sci Techn. 2017; 8(7): 5119-5123.
Kumar ASG, Javvadi RK, Kumar VK, Reddy ME, Reddy VY, Harshavardhan G, Akbar M D. Effect of methanolic extract of Adenanthera pavonina linn on Dalton's Ascitic Lymphoma. Ind J Res Pharma Biotech. 2014; 1(1): 138-141.
Sasikala RP, Meena KS. In Silico Molecular Docking Studies of Multi-Potential Compounds Isolated from Premna Serratifolia L., Inn J Life Sci. 2016; 4(3): 1-7.
Rehman TU, Khan AU, Abbas A, Hussain J, Khan FU, Stieglitz K, Ali S. Investigation of nepetolide as a novel lead compound: Antioxidant, antimicrobial, cytotoxic, anticancer, anti-inflammatory, analgesic activities and molecular docking evaluation. Saud Pharm J. 2018; 26: 422–429.
Singh V, Praveen V, Tripathi D, Haque S, Somvanshi P, Katti SB, Tripathi CKM. Isolation, characterization and antifungal docking studies of wortmannin isolated from Penicillium radicum. Nat Sci Rep. 2015; 5: 11948.
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