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Anti-Infective Agents

Editor-in-Chief

ISSN (Print): 2211-3525
ISSN (Online): 2211-3533

Research Article

Structural Analysis, Antifungal Activity and Molecular Docking Study of a Compound Isolated from Streptomyces species

Author(s): Ajay Kumar*, Anurag Agrawal, Diwakar Chauhan and Pragati Saini

Volume 19, Issue 2, 2021

Published on: 22 October, 2020

Page: [220 - 229] Pages: 10

DOI: 10.2174/2211352518999201022191232

Price: $65

Abstract

Background: The emergence of drug resistance is the biggest threat; consequently, novel antimicrobial agents from natural sources is the need of the hour. This study was designed to isolate and evaluate a bioactive compound from actinomycete against human pathogens.

Methods: In search of a new antimicrobial compound with enhanced potency, several actinomycetes were isolated and screened for their anidermatophytic acitivity. The bioactive compound was extracted and purified by chromatographic technique. The structure of the extracted bio active compound was elucidated by mass and NMR data. The synthesized bioactive compound was further tested for its antidermatophytic activity by the micro broth dilution method.

Results: Streptomyces ARITM 03 was isolated that exhibited antifungal activity against human pathogenic fungi by primary and secondary screening methods. The MIC of bioactive compound was found to be 1250, 312.5 and 2500 μg/ml against tested fungal pathogens A. niger, C. albicans and M. canis, respectively. Chromatography analysis of active metabolite showed a single spot having Rf value of 0.74 and FT-IR spectrum displaying the presence of OH, CO=NH2 functional amide group, and C=O keto groups in the structure. The mass and NMR spectra revealed the molecular formula C26H44N4O6 of bioactive compound. The azole derivative showed an acceptable docking score and exhibited a greater zone of inhibition in comparison to the other compounds.

Conclusion: The results presented in this paper provided an insight into the capability of Streptomyces sp. ARITM03 as a potential source of bioactive secondary metabolites compound a molecule to develop other azoles, to be used clinically to overcome adverse effects like gynecomastia and hepatotoxicity due to extensive use of current azole antifungal agents.

Keywords: Actinomycetes, anti-dermatophytic activity, bioactive metabolites, micro-broth dilution method, NMR, ARITM03.

Graphical Abstract

[1]
Segura, T.; Puga, A.M.; Burillo, G.; Llovo, J.; Brackman, G.; Coenye, T.; Concheiro, A.; Alvarez-Lorenzo, C. Materials with fungi-bioinspired surface for efficient binding and fungi-sensitive release of antifungal agents. Biomacromolecules, 2014, 15(5), 1860-1870.
[http://dx.doi.org/10.1021/bm500257s] [PMID: 24712760]
[2]
Pfaller, M.A.; Diekema, D.J. Epidemiology of invasive candidiasis: a persistent public health problem. Clin. Microbiol. Rev., 2007, 20(1), 133-163.
[http://dx.doi.org/10.1128/CMR.00029-06] [PMID: 17223626]
[3]
Laxminarayan, R.; Duse, A.; Wattal, C.; Zaidi, A.K.; Wertheim, H.F.; Sumpradit, N.; Vlieghe, E.; Hara, G.L.; Gould, I.M.; Goossens, H.; Greko, C.; So, A.D.; Bigdeli, M.; Tomson, G.; Woodhouse, W.; Ombaka, E.; Peralta, A.Q.; Qamar, F.N.; Mir, F.; Kariuki, S.; Bhutta, Z.A.; Coates, A.; Bergstrom, R.; Wright, G.D.; Brown, E.D.; Cars, O. Antibiotic resistance-the need for global solutions. Lancet Infect. Dis., 2013, 13(12), 1057-1098.
[http://dx.doi.org/10.1016/S1473-3099(13)70318-9] [PMID: 24252483]
[4]
Shao, P.L.; Huang, L.M.; Hsueh, P.R. Recent advances and challenges in the treatment of invasive fungal infections. Int. J. Antimicrob. Agents, 2007, 30(6), 487-495.
[http://dx.doi.org/10.1016/j.ijantimicag.2007.07.019] [PMID: 17961990]
[5]
Goldstein, A.O.; Smith, K.M.; Ives, T.J.; Goldstein, B. Mycotic infections. Effective management of conditions involving the skin, hair, and nails. Geriatrics, 2000, 55(5), 40-42, 45-47, 51-52.
[PMID: 10826264]
[6]
Lee, Y.T.; Cui, C.J.; Chow, E.W.; Pue, N.; Lonhienne, T.; Wang, J.G.; Fraser, J.A.; Guddat, L.W. Sulfonylureas have antifungal activity and are potent inhibitors of Candida albicans acetohydroxyacid synthase. J. Med. Chem., 2013, 56(1), 210-219.
[http://dx.doi.org/10.1021/jm301501k] [PMID: 23237384]
[7]
Groll, A.H.; Piscitelli, S.C.; Walsh, T.J. Clinical pharmacology of systemic antifungal agents: a comprehensive review of agents in clinical use, current investigational compounds, and putative targets for antifungal drug development. Adv. Pharmacol., 1998, 44, 343-500.
[http://dx.doi.org/10.1016/S1054-3589(08)60129-5] [PMID: 9547888]
[8]
Yao, b.; Ji, h.; Cao, Y.; Zhou, Y.; Zhu, J.; Lu, J.; Li, Y.; Chen, J.; Zheng, C.; Jiang, Y. Synthesis and antifungal activities of novel 2-aminotetralin derivatives. J. Med. Chem., 2007, 50, 5293-5300.
[http://dx.doi.org/10.1021/jm0701167]
[9]
Luzhetskyy, A.; Pelzer, S.; Bechthold, A.; Owais, M.; Luzhetskyy, A.; Pelzer, S.; Bechthold, A. The future of natural products as a source of new antibiotics. Curr. Opin. Investig. Drugs, 2007, 8(8), 608-613.
[PMID: 17668363]
[10]
Mohanashrinivasan, V.; Sriramkalyan, P.; Subhadradevi, C.; Selvaranjan, E.; Suganthi, V.; Naine, J. Fermentative production of extracellular pigment from Streptomyces coelicolor. Res. J. Biotechnol., 2013, 8(4), 1-4.
[11]
Okoro, C.K.; Brown, R.; Jones, A.L.; Andrews, B.A.; Asenjo, J.A.; Goodfellow, M.; Bull, A.T. Diversity of culturable actinomycetes in hyper-arid soils of the Atacama Desert, Chile. Antonie van Leeuwenhoek, 2009, 95(2), 121-133.
[http://dx.doi.org/10.1007/s10482-008-9295-2] [PMID: 19052913]
[12]
Ghanem, N.B.; Sabry, S.A.; El-Sherif, Z.M.; Abu El-Ela, G.A. Isolation and enumeration of marine actinomycetes from seawater and sediments in Alexandria. J. Gen. Appl. Microbiol., 2000, 46(3), 105-111.
[http://dx.doi.org/10.2323/jgam.46.105] [PMID: 12483583]
[13]
Gebreyohannes, G.; Moges, F.; Sahile, S.; Raja, N. Isolation and characterization of potential antibiotic producing actinomycetes from water and sediments of Lake Tana, Ethiopia. Asian Pac. J. Trop. Biomed., 2013, 3(6), 426-435.
[http://dx.doi.org/10.1016/S2221-1691(13)60092-1] [PMID: 23730554]
[14]
Iliĉ, S.B.; Konstantinoviĉ, S.S.; Todoroviĉ, Z.B.; Laziĉ, M.L.; Veljkoviĉ, V.B.; Jokoviĉ, N.; Radovanoviĉ, B.C. [Characterization and antimicrobial activity of the bioactive metabolites in streptomycete isolates]. Mikrobiologiia, 2007, 76(4), 480-487.
[PMID: 17974204]
[15]
Pandey, B.; Ghimire, P.; Agrawal, V.P. Studies on the antibacterial activity of actinomycetes isolated from Khumbu region of Mount Everest. J. Appl. Microbiol., 2004, 20, 45-54.
[16]
Nanjwade, B.S.; Chandrasekhar, M.; Goudanawar, S.P.; Manvi, P. Isolation and morphological characterization of antibiotic producing actinomycetes. Trop. J. Pharm. Res., 2010, 9(3), 231-236.
[17]
Altschul, S.F.; Madden, T.L.; Schäffer, A.A.; Zhang, J.; Zhang, Z.; Miller, W.; Lipman, D.J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res., 1997, 25(17), 3389-3402.
[http://dx.doi.org/10.1093/nar/25.17.3389] [PMID: 9254694]
[18]
Andrews, J.M. Determination of minimum inhibitory concentrations. J. Antimicrob. Chemother., 2001, 48(Suppl. 1), 5-16.
[http://dx.doi.org/10.1093/jac/48.suppl_1.5] [PMID: 11420333]
[19]
Böhm, H.J. The development of a simple empirical scoring function to estimate the binding constant for a protein-ligand complex of known three-dimensional structure. J. Comput. Aided Mol. Des., 1994, 8(3), 243-256.
[http://dx.doi.org/10.1007/BF00126743] [PMID: 7964925]
[20]
Clark, R.D.; Strizhev, A.; Leonard, J.M.; Blake, J.F.; Matthew, J.B. Consensus scoring for ligand/protein interactions. J. Mol. Graph. Model., 2002, 20(4), 281-295.
[http://dx.doi.org/10.1016/S1093-3263(01)00125-5] [PMID: 11858637]
[21]
Atalan, E.; Manfio, G.P.; Ward, A.C.; Kroppenstedt, R.M.; Goodfellow, M. Biosystematic studies on novel streptomycetes from soil. Antonie van Leeuwenhoek, 2000, 77(4), 337-353.
[http://dx.doi.org/10.1023/A:1002682728517] [PMID: 10959563]
[22]
Sembiring, L.; Ward, A.C.; Goodfellow, M. Selective isolation and characterisation of members of the Streptomyces violaceusniger clade associated with the roots of Paraserianthes falcataria. Antonie van Leeuwenhoek, 2000, 78(3-4), 353-366.
[http://dx.doi.org/10.1023/A:1010226515202] [PMID: 11386358]
[23]
Crawford, D.L.; Lynch, J.M.; Whipps, J.M.; Ousley, M.A. Isolation and characterization of actinomycete antagonists of a fungal root pathogen. Appl. Environ. Microbiol., 1993, 59(11), 3899-3905.
[http://dx.doi.org/10.1128/AEM.59.11.3899-3905.1993] [PMID: 16349093]
[24]
Pirt, S.J.; Righelato, R.C. Effect of growth rate on the synthesis of penicillin by P. chrysogenum in batch and chemostat culture. Appl. Microbiol., 1967, 15(6), 1284-1290.
[http://dx.doi.org/10.1128/AEM.15.6.1284-1290.1967] [PMID: 16349736]
[25]
Narayana, K.J.P.; Vijalakshmi, M.L. Optimization of antimicrobial methods production by Streptomyces albidoflavus. Res. J. Pharmacy, 2008, 2, 4-7.
[26]
Fourati-Ben Fguira, L.; Fotso, S.; Ben Ameur-Mehdi, R.; Mellouli, L.; Laatsch, H. Purification and structure elucidation of antifungal and antibacterial activities of newly isolated Streptomyces sp. strain US80. Res. Microbiol., 2005, 156(3), 341-347.
[http://dx.doi.org/10.1016/j.resmic.2004.10.006] [PMID: 15808937]
[27]
Kataoka, M.; Ueda, K.; Kudo, T.; Seki, T.; Yoshida, T. Application of the variable region in 16S rDNA to create an index for rapid species identification in the genus Streptomyces. FEMS Microbiol. Lett., 1997, 151(2), 249-255.
[http://dx.doi.org/10.1111/j.1574-6968.1997.tb12578.x] [PMID: 9244758]
[28]
Augustine, S.K.; Bhavsar, S.P.; Kapadnis, B.P. A non-polyene antifungal antibiotic from Streptomyces albidoflavus PU 23. J. Biosci., 2005, 30(2), 201-211.
[http://dx.doi.org/10.1007/BF02703700] [PMID: 15886456]
[29]
Gohlke, H.; Hendlich, M.; Klebe, G. Knowledge-based scoring function to predict protein-ligand interactions. J. Mol. Biol., 2000, 295(2), 337-356.
[http://dx.doi.org/10.1006/jmbi.1999.3371] [PMID: 10623530]
[30]
Wang, R.; Lai, L.; Wang, S. Further development and validation of empirical scoring functions for structure based binding affinity prediction. J. Computer Aid Mol. Des, 2000, 16(1), 11-26.
[http://dx.doi.org/10.1023/A:1016357811882]
[31]
Hargrove, T.Y.; Kim, K.; de Nazaré Correia Soeiro, M.; da Silva, C.F.; Batista, D.D.; Batista, M.M.; Yazlovitskaya, E.M.; Waterman, M.R.; Sulikowski, G.A.; Lepesheva, G.I. CYP51 structures and structure-based development of novel, pathogen-specific inhibitory scaffolds. Int. J. Parasitol. Drugs Drug Resist., 2012, 2, 178-186.
[http://dx.doi.org/10.1016/j.ijpddr.2012.06.001] [PMID: 23504044]

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