Synthesis, characterization of isoxazole derivatives and evaluation of their antibacterial, antioxidant and anticancer activity
DOI:
https://doi.org/10.15584/ejcem.2024.2.25Keywords:
antibacterial, antioxidant activity and anticancer potential, isoxazole, pathogenic bacterialAbstract
Introduction and aim. The synthesis of heterocyclic compounds containing oxygen and nitrogen is profoundly intriguing due to their mechanistic implications in both research and development within organic chemistry and drug discovery. The primary aim of this study is to fabricate a range of pharmacologically active drugs containing the isoxazole moiety.
Material and methods. The synthesis of new derivatives of isoxazole was achieved through a one-pot condensation reaction of 2-[(Substituted phenyl)hydrazono]malononitrile (1) and 3-[(Substituted phenyl)azo]-2,4-Pentanedione (2) with sodium acetate and hydroxylamine hydrochloride (1:1) in ethanol. All the compounds were screened for their in vitro antibacterial activity, in vitro antioxidant and anticancer activity. The synthesized compounds underwent characterization through FTIR, 1 H NMR, and 13C NMR analyses, supported by mass spectral data and elemental analysis.
Results. A set of novel isoxazole derivatives was synthesized with a favorable yield. Among compounds 1d, 1e, 2c, 2d, and 2e exhibited notable antioxidant activities. Compounds 1a, 1b, and 1c demonstrated significant anticancer potential against prostate cancer [PC3] cell lines compared to normal HEK cell lines, while 2a displayed the highest inhibitory zone against Escherichia coli.
Conclusion. Novel compounds with multifaceted biological activities have been successfully designed, and a synthetic route to create isoxazole derivatives has been devised and verified.
Supporting Agencies
Financial support from the MM (DU) Education Trust management is available to facilitate the execution of this research.Downloads
References
Doron S, Gorbach SL. Bacterial infections: overview. International Encyclopedia of Public Health. 2008:273. doi: 10.1016/B978-012373960-5.00596-7
Ma M, Cheng Y, Xu Z, et al. Evaluation of polyamidoamine (PAMAM) dendrimers as drug carriers of anti-bacterial drugs using sulfamethoxazole (SMZ) as a model drug. Eur J Med Chem. 2007;42(1):93-98. doi: 10.1016/j.ejmech.2006.07.015
Yanagihara K. Design of anti-bacterial drug and anti-mycobacterial drug for drug delivery system. Curr Pharm Des. 2002;8(6):475-482. doi: 10.2174/1381612023395808
Diana P, Carbone A, Barraja P, Kelter G, Fiebig H, Cirrincione G. Bioorganic & Medicinal Chemistry and 3 , 5-bis ( 3 0 -indolyl ) -isoxazoles , nortopsentin analogues. Bioorg Med Chem. 2010;18(12):4524-4529. doi: 10.1016/j.bmc.2010.04.061
Sethi P, Khare R, Choudhary R. Complexes of pyrimidine thiones: Mechanochemical synthesis and biological evaluation. Asian J Chem. 2020;32(10):2594-2600. doi: 10.14233/ajchem.2020.22813
Pooja S, Pernita D, Gupta GK, Mostafa Sahar I, Simrat K. Synthesis, characterization, anti-bacterial and DNA nicking activity of new complexes of 1-(2,4-dinitrophenylamino)- 4, 4, 6-trimethyl-3, 4-dihydropyrimidine-2-(1H)-thione. Res J Chem Environ. 2018;22(11):73-88.
Joseph L, George M. Evaluation of in vivo and in vitro anti-inflammatory activity of novel isoxazole series. Eur Int J Sci Technol. 2016;5(3):35-42.
Mączyński M, Artym J, Kociȩba M, Kochanowska I, Ryng S, Zimecki M. Anti-inflammatory properties of an isoxazole derivative - MZO-2. Pharmacol Reports. 2016;68(5):894-902. doi: 10.1016/j.pharep.2016.04.017
Huang X, Dong S, Liu H, et al. Design, Synthesis, and Evaluation of Novel Benzo [d] isoxazole Derivatives as Anticonvulsants by Selectively Blocking the Voltage-Gated Sodium ChannelNaV1.1. ACSChemNeurosci. 2022;13(6):834-845.doi: 10.1021/acschemneuro.1c00846
Hawash M, Jaradat N, Abualhasan M, et al. Evaluation of cytotoxic, COX inhibitory, and antimicrobial activities of novel isoxazole-carboxamide derivatives. Lett Drug Des Discov. 2023;20(12):1994-2002. doi: 10.2174/1570180819666220819151002
Pir M, Agirbas H, Budak F, Sahin O. Synthesis, characterization, antimicrobial activity, and QSAR studies of some new 6-substituted phenyl 3-(4-chlorophenyl)-3a,4,8,8a-tetrahydro-[1,3,2]dioxaborepino [5,6-d]isoxazoles. Heteroat Chem. 2017;28(2):1-12. doi: 10.1002/hc.21363
Saravanan G, Alagarsamy V, Dineshkumar P. Synthesis, analgesic, anti-inflammatory and in vitro antimicrobial activities of some novel isoxazole coupled quinazolin-4 (3 H)-one derivatives. Arch Pharm Res. 2021;44:1-11. doi: 10.1007/s12272-013-0262-8
Shahinshavali S, Sreenivasulu R, Guttikonda VR, Kolli D, Rao MVB. Synthesis and Anticancer Activity of Amide Derivatives of 1,2-Isoxazole Combined 1,2,4-Thiadiazole. Russ J Gen Chem. 2019;89(2):324-329. doi: 10.1134/S1070363219020257
Burra S, Voora V, Rao CP, Vijay Kumar P, Kancha RK, David Krupadanam GL. Synthesis of novel forskolin isoxazole derivatives with potent anti-cancer activity against breast cancer cell lines. Bioorganic Med Chem Lett. 2017;27(18):4314-4318. doi: 10.1016/j.bmcl.2017.08.033
Hawash M. Recent advances of tubulin inhibitors targeting the colchicine binding site for cancer therapy. Biomolecules. 2022;12(12):1843. doi: 10.3390/biom12121843
Hawash M, Jaradat N, Eid AM, et al. Synthesis of novel isoxazole–carboxamide derivatives as promising agents for melanoma and targeted nano-emulgel conjugate for improved cellular permeability. BMC Chem. 2022;16(1):1-12. doi: 10.1186/s13065-022-00839-5
Shaik A, Bhandare RR, Palleapati K, Nissankararao S, Kancharlapalli V, Shaik S. Antimicrobial, antioxidant, and anticancer activities of some novel isoxazole ring containing chalcone and dihydropyrazole derivatives. Molecules. 2020;25(5):1047. doi: 10.3390/molecules25051047
Chithra VS, Reji TF, Brindha J. Synthesis and Structure-Activity Relationship Study of Novel Isoxazole derivatives as Promising Antioxidants. Asian J Res Chem. 2018;11(1):65-68. doi: 10.5958/0974-4150.2018.00014.7
Ketan V, Pooja S, Purti M, Anshul B. Antituberculosis activity of pyrazoles. Res J Chem Environ. 2022;26(10):184-198. doi: 10.25303/2610rjce1840198
Abdul Manan MAF, Cordes DB, Slawin AMZ, et al. The Synthesis and Evaluation of Fluoro-, Trifluoromethyl-, and Iodomuscimols as GABA Agonists. Chem - A Eur J. 2017;23(45):10848-10852. doi: 10.1002/chem.201701443.
Rahman MU, Rathore A, Siddiqui AA, Parveen G, Shahar Yar M. Synthesis and antihypertensive screening of new derivatives of quinazolines linked with isoxazole. Biomed Res Int. 2014;2014. doi: 10.1155/2014/739056.
Agrawal N, Mishra P. Synthesis, monoamine oxidase inhibitory activity and computational study of novel isoxazole derivatives as potential antiparkinson agents. Comput Biol Chem. 2019;79:63-72. doi: 10.1016/j.compbiolchem.2019.01.012.
Pedada SR, Yarla NS, Tambade PJ, et al. Synthesis of new secretory phospholipase A2-inhibitory indole containing isoxazole derivatives as anti-inflammatory and anticancer agents. Eur J Med Chem. 2016;112:289-297. doi: 10.1016/j.ejmech.2016.02.025.
Aggarwal R, Bansal A, Mittal A. Synthesis and antimicrobial activity of 3-(2-thienyl)-4-arylazo-5-hydroxy- 5-trifluoromethyl-Δ2-isoxazolines and 3-(2-thienyl)-4-arylazo- 5-trifluoromethylisoxazoles. J Fluor Chem. 2013;145(2010):95-101. doi: 10.1016/j.jfluchem.2012.10.005.
Kryštof V, Cankař P, Fryšová I, et al. 4-Arylazo-3 , 5-diamino-1 H -pyrazole CDK Inhibitors : SAR Study , Crystal Structure in Complex. J Med Chem. 2006;49(22):6500-6509. doi: 10.1021/jm0605740.
Perez C. Antibiotic assay by agar-well diffusion method. Acta Biol Med Exp. 1990;15:113-115.
Garcia EJ, Oldoni TLC, Alencar SM de, Reis A, Loguercio AD, Grande RHM. Antioxidant activity by DPPH assay of potential solutions to be applied on bleached teeth. Braz Dent J. 2012;23:22-27. doi: 10.1590/S0103-64402012000100004.
Arya GC, Kaur K, Jaitak V. Isoxazole derivatives as anticancer agent: A review on synthetic strategies, mechanism of action and SAR studies. Eur J Med Chem. 2021;221:113511. doi: 10.1016/j.ejmech.2021.113511.
Hawash M, Jaradat N, Bawwab N, Salem K, Arafat H. Design, synthesis, and biological evaluation of phenyl - isoxazole - carboxamide derivatives as anticancer agents. Heterocyclic Communications. 2021:133-141. doi: 10.1515/hc-2020-0134
Hawash M, Kahraman DC, Ergun SG, Cetin-Atalay R, Baytas SN. Synthesis of novel indole-isoxazole hybrids and evaluation of their cytotoxic activities on hepatocellular carcinoma cell lines. BMC Chem. 2021;15(1):1-14. doi: 10.1186/s13065-021-00793-8
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 European Journal of Clinical and Experimental Medicine

This work is licensed under a Creative Commons Attribution 4.0 International License.
Our open access policy is in accordance with the Budapest Open Access Initiative (BOAI) definition: this means that articles have free availability on the public Internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from having access to the Internet itself.
All articles are published with free open access under the CC-BY Creative Commons attribution license (the current version is CC-BY, version 4.0). If you submit your paper for publication by the Eur J Clin Exp Med, you agree to have the CC-BY license applied to your work. Under this Open Access license, you, as the author, agree that anyone may download and read the paper for free. In addition, the article may be reused and quoted provided that the original published version is cited. This facilitates freedom in re-use and also ensures that Eur J Clin Exp Med content can be mined without barriers for the research needs.




