MOLECULAR DOCKING STUDY OF FLAVONOID COMPOUNDS AS INHIBITORS OF Î’-KETOACYL ACYL CARRIER PROTEINSYNTHASE II (KAS II) OF PSEUDOMONAS AERUGINOSA

  • Ghalia Sabbagh Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Aleppo Aleppo University Street, Aleppo, Syria
  • Noura Berakdar University of Aleppo

Abstract

Objective: Fatty acid biosynthesis is essential for bacterial survival. Components of this biosynthetic pathway have been identified as attractive targets for the development of new antibacterial agents. β–Ketoacyl acyl carrier protein synthase (KAS) II is a key catalyst in bacterial fatty acid biosynthesis. It is related to control the temperature dependent regulation of fatty acid composition.

Methods: Structure of KasII (FabF) was retrieved from the Protein Data Bank and the structures of flavonoid compounds have been collected from zinc database. Molecular docking and drug likeness studies were performed for those natural compounds to evaluate and analyze the anti-antimicrobial activity.

Results: Finally one compound, Casticin binds to KAS II with the most favorable binding energy (-112.5 kcal/mol) whereas the reference (-92.76 kcal/mol). The fitness score of the compound suggest that this lead can be formulate as an antimicrobial activities drug against gram-negative Pseudomonas aeruginosa.

Conclusions: The results of this study can be implemented in vitro and in vivo in the drug designing pipeline.

 

Keywords: Pseudomonas aeruginosa, Fatty acid synthases, KAS II, Docking, Flavonoids, iGEMDOCK

Downloads

Download data is not yet available.

References

1. Deza MA, Araujo M, Garrido MJ. Inactivation of escherichia coli, listeria monocytogenes, Pseudomonas aeruginosa and staphylococcus aureus on stainless steel and glass surfaces by neutral electrolyzed water. Lett Appl Microbiol 2005;40:341–6.
2. Bell MT. The Use of Natural Products as Potential Anti-Pseudomonas Agents, Seton Hall University Dissertations and Theses. Spring; 2014. p. 5-17.
3. MacDougall C, Harpe SE, Powell JP, Johnson CK, Edmond MB, Polk RE. Pseudomonas aeruginosa, Staphylococcus aureus, and fluoroquinolone use. Emerging Infect Dis 2005;11:1197–10.
4. Fine MJ, Smith MA, Carson CA, Mutha SS, Sankey SS, Weissfeld LA, et al. Prognosis and outcomes of patients with community-acquired pneumonia. A Meta-Analysis. J Am Med Assoc 1996;275;134–41.
5. Strateva T, Yordano D. Pseudomonas aeruginosa–a phenomenon of bacterial resistance. J Med Microbiol 2009; 58:1133–48.
6. Arora D, Jindal N, Kumar R, Romit M. Emerging antibiotic resistance in pseudomonasa challenge. Int J Pharm Pharm Sci 2011;3:1488-91.
7. Leeb M. A shot in the Arm. Nature 2004;431:892-5.
8. Cronan JE Jr, Rock CO. In Escherichia coli and salmonella typhimurium: cellular and molecular biology. American Society for Microbiology Press: Washington, D. C; 1996.
9. Lai CY, Cronan JE. β-ketoacyl-acyl carrier protein synthase III (FabH) is essential for bacterial fatty acid synthesis. J Biol Chem 2003;19:1494-03.
10. Lu YJ, Zhang YM, Rock CO. Product diversity and regulation of type II fatty acid synthases. Biochem Cell Biol 2004;82:145-55.
11. White SW, Zheng J, Zhang YM, Rock. The structural biology of type II fatty acid biosynthesis. Annu Rev Biochem 2005;74:791-31.
12. Tung T, Schweizer HP. Characterization of pseudomonas aeruginosa enoyl-acyl carrier protein reductase (FabI): a target for the antimicrobial triclosan and its role in acylated homoserine lactone synthesis. J Bacteriol 1999;18:5489-97.
13. Yuan Y, Sachdeva M, Leeds JA, Meredith TC. Fatty acid biosynthesis in pseudomonas aeruginosa is initiated by the fab Y Class of β-ketoacyl acyl carrier protein synthases. J Bacteriol 2012;194:5171-84.
14. Zhang H, Machutta A, Tonge PJ. Fatty acid biosynthesis and oxidation, Stony Brook University. Stony Brook, NY, USA, Elsevier Ltd; 2010.
15. Mengying H, Wu T, Pan S, Xu X. Antimicrobial mechanism of flavonoids against escherichia coli ATCC 25922 by model membrane study. Appl Surf Sci 2014;305:515–21.
16. Céliz G, Daz M, Audisio MC. Antibacterial activity of naringin derivatives against pathogenic strains. J Appl Microbiol 2011;111:731–8.
17. Jain A, Sinha P, Neetin S. Desai, Estimation of flavonoid, phenol content and antioxidant potential of indian screw tree (Helicteres Isora L.). Int J Pharm Sci Res 2014;5:1320-30.
18. Kumar S, Pandey AK. Review article chemistry and biological activities of flavonoids hindawi publishing corporation. Sci World J 2013. doi.org/10.1155/2013/162750. [Article in Press]
19. http://www.rcsb.org/pdb/home/home.do. [Last accessed on 01 Apr 2015].
20. http://www.zinc.docking.orgkl. [Last accessed on 01 Apr 2015].
21. Kumar S, Pandey AK. Chemistry and biological activities of flavonoids. Sci World J 2013. doi.org/10.1155/2013/162750. [Article in Press]
22. Agyepong N, Agyare C, Adarkwa-Yiadom M, Gbedema SY. Phytochemical investigation and anti-microbial activity of clausena anisata (Willd). Hook. Afr J Tradit Complementary Altern Med 2014;11:200-9.
23. Awolola GV, Koorbanally NA, Chenia H, Shode FO, Baijnath H. Antibacterial and anti-biofilm activity of flavonoids and triterpenes isolated from the extracts of ficus sansibarica warb. subsp. sansibarica (Moraceae) Extracts. Afr J Tradit Complementary Altern Med 2014;11:124-31.
24. Hummelova J, Rondevaldova J, Balastikova A, Lapcik O, Kokoska L. The relationship between structure and in vitro antibacterial activity of selected isoflavones and their metabolites with special focus on antistaphylococcal effect of demethyltexasin. Biotechnol Appl Microbiol 2015;60:242-7.
25. Morána A, Gutiérreza S, Martínez-Blancoab H, Ferreroab MA, Monteagudo-Meraa A, Rodríguez-Aparicioab LB. Non-toxic plant metabolites regulate staphylococcus viability and biofilm formation: a natural therapeutic strategy useful in the treatment and prevention of skin infections. Biofouling 2014;30:1175-82.
26. Barbosa de Matos R, Braga-de-Souza S, Pena Seara Pitanga B, Amaral da Silva VD, Viana de Jesus EE, Morales Pinheiro A, et al. Flavonoids modulate the proliferation of neospora caninum in glial cell primary cultures. Korean J Parasitol 2014;52:613-9.
27. L´azaro M. Distribution and biological activities of the flavonoid luteolin. Mini Rev Med Chem 2009;9:31-59.
28. Arima H, Ashida H, Danno G. Rutin enhanced antibacterial activities of flavonoids against bacillus cereus and salmonella enteritidis. Biosci Biotechnol Biochem 2002;66:1009-14.
29. Shohaib T, Shafique M, Dhanya N, Madhu C, Divakar. Importance of flavonoides in therapeutics. Int J Nutr Pharmacol 2011;3:1-18.
30. Novy P, Urban J, Leuner O, Vadlejch J, Kokoska L. In vitro synergistic effects of baicalin with oxytetracyclineand tetracycline against staphylococcus aureus. J Antimicrob Chemother 2011;66:1298-300.
31. Urzua A, Modak B, Villarroel L, Torres R, Andrade L, Mendoza L, et al. External flavonoids from heliotropium megalanthum and H. huascoense (Boraginaceae) chemotaxonomic considerations. Bol Soc Chil Quim 2000:45:23-9.
32. Anis S, Bhargava T, Upadhyay H. A review on phytotherapy by morus alba, review article. Int J Pharm Chem Sci 2012;1:1907-10.
33. Liu J, Sridhar J, Foroozesh M. Cytochrome P450 Family 1 Inhibitors and structure-activity relationships. Molecules 2013;18:14470-95.
34. Sultanova N, Makhmoor T, Abilov ZA, Parween Z, Omurkamzinova VB, Atta-ur-Rahman, et al. Antioxidant and antimicrobial activities of tamarix ramosissima. J Ethnopharmacol 2001;78:201-5.
35. Fliniaux O, Corbin C, Ramsay A, Renouard S, Beejmohun V, Doussot J, et al. Microwave-assisted extraction of herbacetin diglucoside from flax (Linum usitatissimum L.) seed cakes and its quantification using an RP-HPLC-UV system. Molecules 2014;19:3025-37.
36. Küçükboyaci N, Bilge Şener B. Two major flavonoids from the fruits of vitex agnus-castus L. Turk J Pharm Sci 2010;7:119-26.
37. Aslam MS, Choudhary BA, Uzair M, Ijaz AS. The genus ranunculus: a phytochemical and ethnopharmacological review. Int J Pharm Pharm Sci 2012;4:15-22.
38. Talib WH, Abu Zarga MH, Mahasneh AM. Antiproliferative, antimicrobial and apoptosis inducing effects of compounds isolated from inula viscosa. Molecules 2012;17:3291-03.
39. Grecco SS, Gimenes L, Ferreira MJP, Romoff P, Favero OA, Zalewski CA, et al. Triterpenoids and phenolic derivatives from baccharis uncinella C. DC. (Asteraceae). Biochem Syst Ecol 2010;38:1234-7.
40. Cushnie TP, Lambm AJ. Antimicrobial activity of flavonoids. Int J Antimicrob Agents 2005;26:343-56.
41. Neeraja C, Hari Krishna P, Sudhakar Reddy C, Giri CC, Rao KV, Reddy VD. Distribution of andrographis species in different districts of andhra pradesh. Natl Acad Sci 2014;85:601-6.
42. Urzua A, Modak B, Villarroel L, Torres R, Andrade L, Mendoza L, et al. External flavonoids from heliotropium megalanthum and H. Huascoense (Boraginaceae) chemotaxonomic considerations. Bol Soc Chil Quim 2000:45:23-9.
43. Balouiri M, Sadiki M, Ouedrhiri W, Farah A, El Abed S, Koraichi SI. Antibacterial activity of extracts from salvia officinalis and rosmarinus officinalis obtained by sonication and maceration methods. Int J Pharm Pharm Sci 2014;6:167-70.
44. Da Silva Filho AA, De Sousa JPB, Soares S. Antimicrobial activity of the extract and isolated compounds from baccharis dracunculifolia D. C. (Asteraceae). Z. Naturforsch C 2008;63:40-6.
45. Lima CC, Lemos RPL, Conserva LM. Dilleniaceae family: an overview of its ethnomedicinal uses, biological and phytochemical profile. J Pharmacogn Phytochem 2014;3:181-04.
46. Metsämuuronen S, Siren H. Antibacterial compounds in predominant trees in finland review. Metsämuuronen and siren. J Bioprocess Biotech 2014;4:1-13.
47. Pal D, Mishra P, Sachan N, Ghosh AK. Biological activities and medicinal properties of cajanus cajan (L) Millsp. J Adv Pharm Technol Res 2011;2:207–14.
48. Wiart C. Goniothalamus species: a source of drugs for the treatment of cancers and bacterial infections. J Evidence-Based Complementary Altern Med 2007;4:299–11.
49. Borik RM. Isolation and structural characterization of a steroidal antimicrobial agent from clerodendrum baronianum. World J Chem 2013;8:48-54.
50. Brand-Garnys EE, Denzer H, Meijer H, Brand HM. Flavonoids: a review for cosmetic application. part I. J Appl Cosmetol 2007;25:93-109.
51. Joung DK, Mun SH, Lee KS. The antibacterial assay of tectorigenin with detergents or ATPase inhibitors against methicillin-resistant staphylococcus aureus. Hindawi 2014. doi.org/10.1155/2014/716509. [Article in Press]
52. Hammami S, Jannet HB, Bergaoui A, Ciavatta L, Cimino G, Mighri Z. Isolation and structure elucidation of a Flavanone, a Flavanone glycoside and vomifoliol from echiochilon fruticosum growing in tunisia. Molecules 2004;9:602-8.
53. Bastos MLA, Lima MRF, Conserva LM, Andrade VS, Rocha EM, Lemos RP. Studies on the antimicrobial activity and brine shrimp toxicity of zeyheria tuberculosa (Vell.) Bur. (Bignoniaceae) extracts and their main constituents. Ann Clin Microbiol Antimicrob 2009;8:16.
54. Singh MK, Khare G, Iyer SK, Sharwan G, Tripathi DK. Clerodendrum serratum: a clinical approach. Int J Pharm Sci 2012;02:11-5.
55. Filho AAO, Fernandes HMB, Sousa JP, Maia GLA, Barbosa-Filho JM, Lima EO, Oliveira TL. Actividad antibacterial del flavonoide 5.7.4’-Trimetoxiflavona aislada de Prexelis clematides R. M. King and Robinson. Bol Latinoam Caribe Plant Med Aromat 2013;12:400-4.
56. Gargala G, Baishanbo A, FavennecL, François A, Ballet J, Rossignol JF. Inhibitory activities of epidermal growth factor receptor tyrosine kinase-targeted dihydroxyisoflavone and trihydroxydeoxybenzoin derivatives on sarcocystis neurona, Neospora caninum, and cryptosporidium parvum development. Antimicrob Agents Chemother 2005;49:4628–34.
57. Liu G, Liang JC, Wang XL, Li ZH, Wang W, Guo N, et al. In vitro synergy of biochanin a and ciprofloxacin against clinical isolates of staphylococcus aureus. Molecules 2011;16:6656-66.
58. Johari SA, Kiong LS, Mohtar M, Isa MM, Man S, Mustafa S, et al. Efflux inhibitory activity of flavonoids from chromolaena odorata against selected methicillin resistant staphylococcus aureus (MRSA) isolates. Afr J Microbiol Res 2012;6:5631-5.
59. Azlan A, Younis L, Mahmud NH, Dardiri NA. Mechanisms of action of andrographis paniculata as anti-atherosclerotic agent. Eur Int J Sci 2013;2:91-6.
60. Bell MT. The Use of Natural Products as Potential Anti-Pseudomonas Agents, Seton Hall University Dissertations and Theses. Spring; 2014. p. 5-17.
61. Wright HT, Reynolds KA. Antibacterial targets in fatty acid biosynthesis. Curr Opin Microbiol 2007;10:447–53.
62. Tapas AR, Sakarka DM, Kakde RB. Flavonoids as nutraceuticals. Trop J Pharm Res 2008;7:1089-99.
63. Gnanslin Sheeba D, Subha V, Suseela Gomathi K, Citarasu T. Virtual docking studies of flavonoid compounds against cell wall proteins of mycobacterium tuberculosis. Asian J Pharm Res Dev 2013;1:88-97.
64. Bugata BK, Kaladhar DSVGK. QSAR and docking studies of synthesized diarylsulfonylurea chalcone hybrids as anti-inflammatory agents. Int J Pharm Sci Rev Res 2014;24:144-9.
65. Chen CC, Er TK, Liu YY, Hwang JK, Barrio MJ, Rodrigo M, et al. Computational analysis of KRAS mutations: implications for different effects on the KRAS p. G12D and p. G13D mutations. PLoS One 2013;8:e55793.
66. Kai CH, Yen FC, Shen RL, Jinn MY. IGEMDOCK: a graphical environment of enhancing GEMDOCK using pharmacological interactions and postscreening analysis. BMC Bioinf 2011;12(Suppl 1):S33.
67. Yang JM. Graphical-Automatic Drug Design System for Docking, Screening and Post-Analysis. Department of Biological Science and Technology and Institute of Bioinformatics National Chiao Tung University; 2008. p. 1-69.
68. 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 2001;46:3–26.
69. Thomas G. Medicinal chemistry. 2nd Edition. University of Portsmouth; 2007. p. 9-10.
70. Kerns EH, Di L. Drug-like properties: concepts, structure design and methods: from ADME to toxicity optimization. Academic Press is an imprint of Elsevier; 2008. p. 6-120.
71. 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 2001;46:3–26.
72. Zhang YM, White SW, Rock CO. Inhibiting bacterial fatty acid synthesis. J Biol Chem 2006;281:17541-4.
Statistics
565 Views | 1903 Downloads
How to Cite
Sabbagh, G., and N. Berakdar. “MOLECULAR DOCKING STUDY OF FLAVONOID COMPOUNDS AS INHIBITORS OF Î’-KETOACYL ACYL CARRIER PROTEINSYNTHASE II (KAS II) OF PSEUDOMONAS AERUGINOSA”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 8, no. 1, Nov. 2015, pp. 52-61, https://innovareacademics.in/journals/index.php/ijpps/article/view/8214.
Section
Original Article(s)