Synthesis, Antibacterial and Antioxidant Evaluation of 2-Substituted-4-arylidene-5(4H)-oxazolone Derivatives

https://doi.org/10.22146/ijc.83052

Lina Saadi(1*), Shaimaa Adnan(2)

(1) Department of Pharmaceutical Chemistry, College of Pharmacy, University of Al-Qadisiyah, Diwaniyah 58001, Iraq
(2) Department of Chemistry, College of Education, University of Al-Qadisiyah, Diwaniyah 58001, Iraq
(*) Corresponding Author

Abstract


In this research, the synthesis of new substituted oxazolone derivatives is described via Erlenmeyer synthesis of N-acyl amino acid. Firstly, the azo derivative 1 was prepared by coupling the diazonium salt of 3-amino-4-methoxybenzoic acid with 4,5-dichloroimidazole in sodium hydroxide solution. Benzoyl chloride derivative 2, the key intermediate of the synthesis, was synthesized by the acylation of azo-carboxylic acid derivative 1 with thionyl chloride. The resulting acyl chloride derivative reacted with glycine in a basic catalyst to form a hippuric acid derivative 3. After that, oxazolone derivatives 4a4f were prepared via the reaction of the hippuric acid derivative with various aromatic aldehydes. All new compound structures were confirmed by spectral techniques, i.e., FTIR, 1H-NMR, 13C-NMR spectroscopy, and elemental analysis. The antimicrobial activity (Staphylococcus aureus and Escherichia coli) of all new compounds was screened in vitro. The results against S. aureus and E. coli showed that most of the tested compounds have an activity ranging from moderate to low. The antioxidant activity of derivative 4a was also evaluated and showed good antioxidant activity.


Keywords


antibacterial; antioxidants; Erlenmeyer reaction; glycine; oxazolone

Full Text:

Full Text PDF


References

[1] Kushwaha, N., and Kushwaha, S., 2021, Synthetic approaches and biological significance of oxazolone moieties: A review, Biointerface Res. Appl. Chem., 12 (5), 6460–6486.‏

[2] Rodrigues, C.A.B., Martinho, J.M.G., and Afonso, C.A.M., 2015, Synthesis of a biologically active oxazol-5-(4H)-one via an Erlenmeyer–Plöchl reaction, J. Chem. Educ., 92 (9), 1543–1546.‏

[3] Hammouda, M.B., Boudriga, S., Hamden, K., Askri, M., Knorr, M., Strohmann, C., Brieger, L., Krupp, A., Anouar, E.H., Snoussi, M., Aouadi, K., and Kadri, A., 2022, New spiropyrrolothiazole derivatives bearing an oxazolone moiety as potential antidiabetic agent: Design, synthesis, crystal structure, Hirshfeld surface analysis, ADME and molecular docking studies, J. Mol. Struct., 1254, 132398.‏

[4] Almalki, A.J., Ibrahim, T.S., Taher, E.S., Mohamed, M.F.A., Youns, M., Hegazy, W.A., and Al-Mahmoudy, A.M.M., 2022, Synthesis, antimicrobial, anti-virulence and anticancer evaluation of new 5(4H)-oxazolone-based sulfonamides, Molecules, 27 (3), 671.

[5] Algohary, A.M., and Alhalafi, M.H., 2022., Design, synthesis and evaluate of imidazole, triazine and metastable oxazolone derivatives as chemosensor for detecting metals, J. Saudi Chem. Soc., 26 (6), 101537.‏

[6] Zhou, B., and Chen, W., 2013, The zwitterionic imidazolium salt: First used for synthesis of 4-arylidene-2-phenyl-5(4H)-oxazolones under solvent-free conditions, J. Chem., 2013, 280585.

[7] Parveen, M., Ali, A., Ahmed, S., Malla, A.M., Alam, M., Pereira Silva, P.S., Silva, M.R., and Lee, D.U., 2013, Synthesis, bioassay, crystal structure and ab initio studies of Erlenmeyer azlactones, Spectrochim. Acta, Part A, 104, 538–545.‏

[8] Alghamdi, S.S., Suliman, R.S., Alshehri, R.A., Almahmoud, R.S., and Alhujirey, R.I., 2022, N-heterocycle derivatives: An update on the biological activity in correlation with computational predictions, J. Appl. Pharm. Sci., 12 (5), 59–77.‏

[9] Ahmed, N.G., and Hamad, A.N., 2023, Synthesis and preliminary pharmacological profile of some new 3,5-dihydro-4H-imidazol-4-one and α,β-dehydroamino acid derivatives, Zanco J. Pure Appl. Sci., 35 (1), 223–240.‏

[10] Jadhav, S.A., Sarkate, A.P., Farooqui, M., and Shinde, D.B., 2017, Greener approach: Ionic liquid [Et3NH][HSO4]-catalyzed multicomponent synthesis of 4-arylidene-2-phenyl-5(4H) oxazolones under solvent-free condition, Synth. Commun., 47 (18), 1676–1683.‏

[11] Mobinikhaledi, A., Moghanian, H., and Pakdel, S., 2015, Microwave-assisted efficient synthesis of azlactone derivatives using 2-aminopyridine-functionalized sphere SiO2 nanoparticles as a reusable heterogeneous catalyst, Chin. Chem. Lett., 26 (5), 557–563.‏

[12] Fadda, A.A., Mohammed, R.M., Tawfik, E.H., and Hammouda, M.A., 2021, Synthesis and anticancer activity of new 2-aryl-4-(4-methoxybenzylidene)-5-oxazolone scaffolds, Biointerface Res. Appl. Chem., 11 (1), 8096–8109.‏

[13] Gaba, M., and Mohan, C., 2016, Development of drugs based on imidazole and benzimidazole bioactive heterocycles: Recent advances and future directions, Med. Chem. Res., 25 (2), 173–210.‏

[14] Saudi, M., Zmurko, J., Kaptein, S., Rozenski, J., Neyts, J., and Van Aerschot, A., 2014, Synthesis and evaluation of imidazole-4,5- and pyrazine-2,3-dicarboxamides targeting dengue and yellow fever virus, Eur. J. Med. Chem., 87, 529–539.‏

[15] Aleksandrova, E.V., Kravchenko, A.N., and Kochergin, P.M., 2011, Properties of haloimidazoles (review), Chem. Heterocycl. Comp., 47 (3), 261–289.‏

[16] Peng, X.M., LV Damu, G., and Zhou, C.H., 2013, Current developments of coumarin compounds in medicinal chemistry, Curr. Pharm. Des., 19 (21), 3884–3930.‏

[17] Shridhar, A.H., Keshavayya, J., Peethambar, S.K., and Joy Hoskeri, H., 2016, Synthesis and biological activities of bis alkyl 1,3,4-oxadiazole incorporated azo dye derivatives, Arabian J. Chem., 9 (Suppl. 2), S1643–S1648.‏

[18] Gaber, M., El-Sayed, Y.S., El-Baradie, K.Y., and Fahmy, R.M., 2013, Complex formation, thermal behavior and stability competition between Cu(II) ion and Cu0 nanoparticles with some new azo dyes. Antioxidant and in vitro cytotoxic activity, Spectrochim. Acta, Part A, 107, 359–370.

[19] Rizk, H.F., Ibrahim, S.A., and El-Borai, M.A., 2017, Synthesis, dyeing performance on polyester fiber and antimicrobial studies of some novel pyrazolotriazine and pyrazolyl pyrazolone azo dyes, Arabian J. Chem., 10 (Suppl. 2), S3303–S3309.‏

[20] Dhaef, H.K., Al-Asadi, R.H., Shenta, A.A., and Mohammed, M.K., 2021, Novel bis maleimide derivatives containing azo group: Synthesis, corrosion inhibition, and theoretical study, Indones. J. Chem., 21 (5), 1212–1220.‏

[21] Yahya, W.I., Mgheed, T.H., and Kadhium, A.J., 2022, Preparation, characterization of some metal complexes of new mixed ligands derived from 5-methyl imidazole and study the biological activity of palladium(II) complex as anticance, NeuroQuantology, 20 (1), 71–83.‏

[22] El Newahie, A.M.S., Nissan, Y.M., Ismail, N.S., Abou El Ella, D.A., Khojah, S.M., and Abouzid, K.A.M., 2019, Design and synthesis of new quinoxaline derivatives as anticancer agents and apoptotic inducers, Molecules, 24 (6), 1175.‏

[23] Abdul-Amir, R.M., Al-Hassan, N.M.A., and Ghadban, H., 2021, Synthesis of some new heterocyclic compounds derived from p-chlorobenzoylchloride and investigation of biological effectiveness, J. Phys.: Conf. Ser., 1853 (1), 012009.

[24] Dube, P.N., Mokale, S.N., Shaikh, S.I., Patil, Y., Yadav, B., Deshmukh, P., and Sabde, S., 2015, Synthesis and molecular docking analysis of imidazol-5-one derivatives as anti-HIV NNRTIs, Pharm. Chem. J., 49 (2), 125–131.‏

[25] Mollea, C., Bosco, F., and Fissore, D., 2022, Agar plate methods for assessing the antibacterial activity of thyme and oregano essential oils against S. epidermidis and E. coli, Antibiotics, 11 (12), 1809.‏

[26] Ali, A.T., Mosa, M.N., Alshaheen, Z.G., and Muhammad-Ali, M.A., 2020, Synthesis, characterization and antibacterial evaluation of oxoazetidine - benzene sulfonamide derivatives as a hybrid antimicrobial agent, Syst. Rev. Pharm., 11 (2), 487–494.‏

[27] Al-Joufi, F.A., Salem-Bekhit, M.M., Taha, E.I., Ibrahim, M.A., Muharram, M.M., Alshehri, S., Ghoneim, M.M., and Shakeel, F., 2022, Enhancing ocular bioavailability of ciprofloxacin using colloidal lipid-based carrier for the management of post-surgical infection, Molecules, 27 (3), 733.

[28] Kim, G., Gan, R.Y., Zhang, D., Farha, A.K., Habimana, O., Mavumengwana, V., Li, H.B., Wang, X.H., and Corke, H., 2020, Large-scale screening of 239 traditional Chinese medicinal plant extracts for their antibacterial activities against multidrug-resistant Staphylococcus aureus and cytotoxic activities, Pathogens, 9 (3), 185–203.‏

[29] Dvornikova, I.A., Buravlev, E.V., Fedorova, I.V., Shevchenko, O.G., Chukicheva, I.Y., and Kutchin, A.V., 2019, Synthesis and antioxidant properties of benzimidazole derivatives with isobornylphenol fragments, Russ. Chem. Bull., 68 (5), 1000–1005.‏

[30] Tiéba, T.N., Baptiste, K.N.J., Daouda, B., Claude, K.A.L., Guillaume, K.C., Bernard, Y.O., and Nahossé, Z., 2021, Antioxidant activity evaluation in a series of heterocyclic compounds derived from 1,8-diaminonaphthalene, J. Biophys. Chem., 12 (1), 1–9.‏

[31] Kizilkaya, H., Dag, B., Aral, T., Genc, N., and Erenler, R., 2020, Synthesis, characterization, and antioxidant activity of heterocyclic Schiff bases, J. Chin. Chem. Soc., 67 (9), 1696–1701.‏



DOI: https://doi.org/10.22146/ijc.83052

Article Metrics

Abstract views : 518 | views : 228


Copyright (c) 2023 Indonesian Journal of Chemistry

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

 


Indonesian Journal of Chemistry (ISSN 1411-9420 /e-ISSN 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.

Web
Analytics View The Statistics of Indones. J. Chem.