SYNTHESIS, IN SILICO STUDIES AND EVALUATION OF ANTIBACTERIAL ACTIVITY OF 4-SUBSTITUTED BENZYLIDENE-2-(PHENOXYMETHYL) OXAZOL-5(4H)-ONES

  • SHAHEEN BEGUM Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupati, Andhra Pradesh, India.
  • ARIFA BEGUM SK Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupati, Andhra Pradesh, India.
  • MANEESHA M Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupati, Andhra Pradesh, India.
  • OME SHANTHI T Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupati, Andhra Pradesh, India.
  • SATYA VARALAKSHMI D Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupati, Andhra Pradesh, India.
  • MANJUSHA RK Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupati, Andhra Pradesh, India.
  • BHARATHI K Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupati, Andhra Pradesh, India.
  • BHARATHI K Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupati, Andhra Pradesh, India.

Abstract

Objective: Arylidene-1, 3-oxazol-5-ones represent potential antibacterial agents. In the present work, a series of 4-substituted benzylidene-2- (phenoxymethyl) oxazol-5(4H)-ones were synthesized and screened for antibacterial activity against Gram-negative bacteria Escherichia coli. To explore plausible mechanisms, synthesized compounds were docked with DNA-Gyrase enzyme.


Methods: All the reactants, phenoxy acetyl chloride, acetic anhydride, sodium acetate, substituted aromatic aldehydes, and glycine were triturated in a mortar by mechanical stirring. The antibacterial potentiality of the compounds was screened against E. coli using the disk diffusion method and the activity was recorded as a zone of inhibition.


Results: Compound 2d, possessing 3, 4, 5-trimethoxy functionality on benzylidene ring exhibited the highest activity with 19 mm of the zone of inhibition which might be due to its higher interactions with DNA-Gyrase enzyme (ΔG-8.41 kcal/mol). Compounds 2a, 2b, and 2c exhibited moderate activity in the antimicrobial assay as well as in docking study indicating the positive contribution of substitution on benzylidene ring.


Conclusion: A series of 4-substituted benzylidene-2-(phenoxymethyl) oxazol-5(4H)-ones were synthesized and evaluated for antibacterial activity. Compounds 2a, 2b, and 2c displayed moderate activity whereas 2d showed maximum zone of inhibition (19 mm). The good activity of these derivatives presumed to be due to the conformational flexibility of phenoxy methylene moiety which can be well accommodated in the target binding site.

Keywords: 4-Benzylidene-2-(phenoxymethyl) oxazol-5(4H)-ones, Molecular docking, DNA-Gyrase, Cup-plate method, Molecular properties.

References

1. Mukherjee S. Emerging infectious diseases: Epidemiological perspective. Indian J Dermatol 2017;62:459-67.
2. Noel GJ, Draper MP, Hait H, Tanaka SK, Arbeit RD. A randomized, evaluator-blind, phase 2 study comparing the safety and efficacy of omadacycline to those of linezolid for treatment of complicated skin and skin structure infections. Antimicrob Agents Chemother 2012;56:5650-4.
3. Lin J, Nishino K, Roberts MC, Tolmasky M, Aminov RI, Zhang L, et al. Mechanisms of antibiotic resistance. Front Microbiol 2015;6:1-3.
4. Brown ED, Wright GD. Antibacterial drug discovery in the resistance era. Nature 2016;529:336-43.
5. Chandra H, Bishnoi P, Yadav A, Patni B, Mishra AP, Nautiyal AR, et al. Antimicrobial resistance and the alternative resources with special emphasis on plant-based antimicrobials-a review. Plants 2017;6:1-11.
6. Haque M. Antimicrobial use, prescribing, and resistance in selected ten selected developing countries: A brief overview. Asian J Pharm Clin Res 2017;10:37-45.
7. El-Gamal KM, Sherbiny FF, El-Morsi AM, Abu-El-Khair HE, Eissa IH, El-Sebaei MM. Design, synthesis and antimicrobial evaluation of some novel quinoline derivatives. Pharm Pharmacol Int J 2015;2:165-77.
8. Onkol T, Do?ruer DS, Uzun L, Adak S, Ozkan S, Sahin MF, et al. Synthesis and antimicrobial activity of new 1,2,4-triazole and 1,3,4-thiadiazole derivatives. J Enzyme Inhib Med Chem 2008;23:277-84.
9. El-Salam NM, Mostafa MS, Ahmed GA, Alothman OY. Synthesis and antimicrobial activities of some new heterocyclic compounds based on 6-chloropyridazine-3 (2H) -thione. J Chem 2013;13:1-8.
10. Sharma R. Review: Antimicrobial agents based on nitrogen and sulfur containing heterocycles. Asian J Pharm Clin Res 2017;10:47-9.
11. Rajitha G, Prasad KV, Bharathi K. Synthesis and biological evaluation of 3-amino pyrazolones. Asian J Chem 2011;23:684-6.
12. Bala S, Saini M, Sunil K. Methods for synthesis of oxazolones: A review. Int J Chemtech Res 2011;3:1102-18.
13. Sharada LN, Aparna Y, Saba M, Sunitha SN, Viveka L. A review on reactions and applications of oxazolones. Int J Sci Res 2015;5:1-9.
14. El-Mekabaty A. Erlenmeyer azlactones: Synthesis, reactions and biological activity. Int J Mod Org Chem 2013;2:40-66.
15. Mariappan G, Saha BP, Datta S, Kumar D, Haldar PK. Design, synthesis and antidiabetic evaluation of oxazolone derivatives. J Chem Sci 2011;123:335-41.
16. Al-Ghabkari A, Deng JT, McDonald PC, Dedhar S, Alshehri M, Walsh MP, et al. A novel inhibitory effect of oxazol-5-one compounds on ROCKII signaling in human coronary artery vascular smooth muscle cells. Sci Rep 2016;6:32118.
17. Jat LR, Mishra R, Pathak D. Synthesis and anticancer activity of 4-benzylidene-2- phenyloxazol-5(4h)-one derivatives. Int J Pharm Pharm Sci 2012;4:378-80.
18. Saravanan VS, Selvan PS, Gopal N, De B, Gupta JK. Synthesis and antibacterial activity of some 4-substituted-2-phenyl oxazol-5(4H)-one derivatives. Asian J Chem 2006;18:2511-4.
19. Bayoumi WA, Shaymaa HA, Mohamed ES. Synthesis and evaluation of new 2-iminothiazolidin-4-one and thiazolidin-2, 4-dione derivatives as antimicrobial and anti-inflammatory agents. Open Chem J 2014;1:33-8.
20. Ottana R, Maccari R, Barreca ML, Bruno G, Rotondo A, Rossi A, et al. 5-Arylidene-2-imino-4-thiazolidinones: Design and synthesis of novel anti-inflammatory agents. Bioorg Med Chem 2005;13:134243-52.
21. Vicini P, Zani F, Cozzini P, Doytchinova I. Hydrazones of 1,2-benzisothiazole hydrazides: Synthesis, antimicrobial activity and QSAR investigations. Eur J Med Chem 2002;37:553-64.
22. Amjid I, Hamid LS, Ashraf CM, Ahmad M, Weaver GW. Synthesis, characterization and antibacterial activity of azomethine derivatives derived from 2-formylphenoxyacetic acid. Molecules 2007;12:245-54.
23. Pattan SR, Hullolikar RL, Pattan JS, Kapadnis BP, Dighe NS, Dengale SS. Synthesis and evaluation of some new pyrazolo phenoxy acetic acid derivatives for their antitubercular activity. J Pharm Sci Res 2009;1:63-8.
24. Aaglawe MJ, Dhule SS, Bahekar SS, Wakte PS, Shinde DB. Synthesis and antibacterial activity of some oxazolone derivatives. J Korean Chem Soc 2003;47:133-6.
25. Varma RS. Greener chemical syntheses using mechanochemical mixing or microwave and ultrasound irradiation. Green Chem Lett Rev 2007;1:37-45.
26. Leonardi M, Villacampa M, Menéndez JC. Multicomponent mechanochemical synthesis. Chem Sci 2018;9:2042-64.
27. El-Sayed AA, Hemdan MM, Fahmy AF. Multicomponent synthesis of 4-arylidene-2-phenyl-5(4H)-oxazolones (azlactones) using a mechanochemical approach. Chem Cent J 2016;10:1-7.
28. Rajitha G, Prasad KV, Bharathi K. Synthesis and evaluation of substituted cinnamoyl alanines for antiinflammatory, analgesic and antioxidant activities. Asian J Chem 2010;22:1197-04.
29. Grosdidier A, Zoete V, Michielin O. SwissDock, a protein-small molecule docking web service based on EADock DSS. Nucleic Acids Res 2011;39:W270-7.
30. Soujanya M, Rajitha G. Microwave assisted synthesis, characterization, molecular docking and antimicrobial evaluation of 4-nitrocinnamide analogues. Int J Pharm Sci Res 2017;8:3786-94.
31. Walker SS, Labroli M, Painter RE, Wiltsie J, Sherborne B, Murgolo N, et al. Antibacterial small molecules targeting the conserved TOPRIM domain of DNA gyrase. PLoS One 2017;12:e0180965.
32. Mayer C, Janin YL. Non-quinolone inhibitors of bacterial Type IIA topoisomerases: A feat of bioisosterism. Chem Rev 2014;114:2313-42.
33. Basarab GS, Brassil P, Doig P, Galullo V, Haimes HB, Kern G. Novel DNA gyrase inhibiting spiropyrimidinetriones with a benzisoxazole scaffold: SAR and in vivo characterization. J Med Chem 2014;57:
9078-95.
34. Manjusha RK, Begum A, Swapna B, Begum S, Bharathi K, Sujatha D. Molecular docking studies of 4-benzylidene-2-(4-hydroxy-3- methoxystyryl) oxazol-5(4H)-ones; Interactions with Arg-136 and Asp-73 of DNA gyrase. J Glob Trends Pharm Sci 2018;9:
5172-80.
35. Abolhasani H, Zarghi A, Hamzeh-Mivehroud M, Alizadeh AA, Mojarrad SD. In-silico investigation of tubulin binding modes of a series of novel antiproliferative spiroisoxazoline compounds using docking studies. Iran J Pharm Res 2015;14:141-7.
Statistics
169 Views | 44 Downloads
How to Cite
SHAHEEN BEGUM, ARIFA BEGUM SK, MANEESHA M, OME SHANTHI T, SATYA VARALAKSHMI D, MANJUSHA RK, BHARATHI K, and BHARATHI K. “SYNTHESIS, IN SILICO STUDIES AND EVALUATION OF ANTIBACTERIAL ACTIVITY OF 4-SUBSTITUTED BENZYLIDENE-2-(PHENOXYMETHYL) OXAZOL-5(4H)-ONES”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 12, no. 5, Apr. 2019, pp. 282-8, https://innovareacademics.in/journals/index.php/ajpcr/article/view/31390.
Section
Original Article(s)