Design and Synthesis of Novel Isoxazole Derivatives with Enhanced Analgesic & Antimicrobial Activity

Authors

Girendra Kumar Gautam

Department of Pharmaceutical Chemistry, Shri Ram College of Pharmacy, Muzaffarnagar-251001, U.P. (India)

Mohan Kumar

Department of Pharmaceutical Chemistry, Shri Ram College of Pharmacy, Muzaffarnagar-251001, U.P. (India)

Vaishali

Department of Pharmaceutical Chemistry, SD College of Pharmacy & Vocational Studies, Muzaffarnagar-251001, U.P. (India)

Kuldeep Saini

Department of Pharmaceutical Chemistry, SD College of Pharmacy & Vocational Studies, Muzaffarnagar-251001, U.P. (India)

Vikul Kumar

Department of Pharmaceutical Chemistry, SD College of Pharmacy & Vocational Studies, Muzaffarnagar-251001, U.P. (India)

Akansha Nirwal

Department of Pharmaceutics, Shri Ram Group of College, Muzaffarnagar-251001, U.P. (India)

Ravi Kumar

Department of Pharmacology, SD College of Pharmacy & Vocational Studies, Muzaffarnagar-251001, U.P. (India)

Article Information

DOI: 10.51584/IJRIAS.2026.11060179

Subject Category: Pharmacy

Volume/Issue: 11/6 | Page No: 2346-2358

Publication Timeline

Submitted: 2026-06-17

Accepted: 2026-06-22

Published: 2026-07-07

Abstract

Background: Isoxazole compounds have demonstrated interesting pharmacological properties, such as AMPA receptor ligand activity, anticancer, anti-inflammatory, and Immunoregulatory effects. The amazing pharmacological uses of Isoxazoles derivatives, including their antibacterial, antiviral, antiplatelet, analgesic, anti nociceptive, anticonvulsant, COX-2 inhibitory, and immunological modulating properties. Materials and Methods: Isoxazole derivatives produced using the Claisen-Schmidt method to get Chalcones, the condensation process was used. Chalcones were created via Acetophenone condensation with aldehyde in the presence of a base. Chalcones were reacted with potassium hydroxide and hydroxyl amine hydrochloric acid to get an Isoxazole derivative. We tested to the new synthesized Isoxazoles derivatives by the analyzing method of 1HNMR and FTIR We investigated the analgesic and bactericidal properties of these compounds. This study endeavor has looked at the synthesis of new Isoxazoles using a variety of substituted Chalcone. Results: The potential medicinal applications of Isoxazoles derivatives have been explored through the screening of these new compounds for their antibacterial and Alagesic activities. Conclusion: Isoxazoles compounds have shown to be effective against a variety of biological targets, they are frequently used as building blocks for the creation of novel drugs. These substances have demonstrated potential as analgesic and antibacterial agents

Keywords

Chalcone, Isoxazole derivatives, analgesic activity, Antibacterial

Downloads

References

1. Chikkula KV, Sundararajan R. Analgesic, anti-inflammatory, and antimicrobial activities of novel isoxazole/pyrimidine/pyrazole substituted benzimidazole analogs. Med Chem Res. 2017;26(11):3026-37. doi: 10.1007/s00044-017-2000-0. [Google Scholar] [Crossref]

2. Sahu SK, Banerjee M, Sahu D, Behera C, Pradhan G, Azam MA. Synthesis, analgesic and antimicrobial activities of some novel isoxazole derivatives. Dhaka Univ J Pharm Sci. 2008;7(2):113-8. doi: 10.3329/dujps.v7i2.2165. [Google Scholar] [Crossref]

3. Praveen C, Kalyanasundaram A, Perumal PT. Gold(III)-catalyzed synthesis of isoxazoles by cycloisomerization of α, β-acetylenic oximes. Synlett 2010.05. 2010:777-81. [Google Scholar] [Crossref]

4. Kadam KS, et al. Alkyl nitrites: novel reagents for one-pot synthesis of 3, 5-disubstituted isoxazoles from aldoximes and alkynes. Synthesis. 2016:3996-4008. [Google Scholar] [Crossref]

5. Zhu J, Mo J, Lin HZ, Chen Y, Sun HP. The recent progress of isoxazole in medicinal chemistry. Bioorg Med Chem. 2018;26(12):3065-75. doi: 10.1016/j.bmc.2018.05.013, PMID 29853341. [Google Scholar] [Crossref]

6. Isoxazole–a potent pharmacophore International Journal of Pharmacy and Pharmaceutical Sciences Chikkula. Krishna Veni, and S. Raja. 2017: 13-24. [Google Scholar] [Crossref]

7. Shaik, Afzal, et al., 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 25.5. (2020);25(5): 1047. doi: 10.3390/molecules25051047, PMID 32110945. [Google Scholar] [Crossref]

8. Hawash M, Jaradat N, Eid AM, Abubaker A, Mufleh O, Al-Hroub Q, 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):47. doi: 10.1186/s13065-022-00839-5, PMID 35751124. [Google Scholar] [Crossref]

9. TL, Sheeja M, Mathew A, Varkey J. Design, synthesis and pharmacological evaluation of isoxazole analogues derived from natural piperine. Asian J Pharm Health Sci. 2012:2.1. [Google Scholar] [Crossref]

10. Morita T, Fuse S, Nakamura H. Photochemical conversion of isoxazoles to 5-Hydroxyimidazolines. Org Lett. 2020;22(9):3460-3. doi: [Google Scholar] [Crossref]

11. Zhu X-Q, Wang ZS, Hou BS, Zhang HW, Deng C, Ye LW. Zinc‐Catalyzed Asymmetric Formal [4+ 3] Annulation of isoxazoles with Enynol Ethers by 6π Electrocyclization: stereoselective Access to 2H‐Azepines. Angew Chem Int Ed Engl. 2020;59(4):1666-73. doi: 10.1002/anie.201912534, PMID 31724314. [Google Scholar] [Crossref]

12. Gautam KC, SinghDP. Synthesis and antimicrobial activity of some isoxazole derivatives of thiophene. Chem SciTrans. 2013;3(3):992-6. [Google Scholar] [Crossref]

13. Sonawane DR, Jaju JB, Pawar GR, Gosavi PA. Evaluation of analgesic and anti-inflammatory activity of levocetirizine in albino rats. Int J Basic Clin Pharmacol. 2019;8(8). doi: 10.18203/2319-2003.ijbcp20193182. [Google Scholar] [Crossref]

14. Balouiri M, Sadiki M, Ibnsouda SK. Methods for in vitro evaluating antimicrobial activity: a review. J Pharm Anal. 2016;6(2):71-9. doi: 10.1016/j.jpha.2015.11.005, PMID 29403965. [Google Scholar] [Crossref]

15. Thakur A, Verma M, Setia P, Bharti R, Sharma R, Sharma A, et al. DFT analysis and in vitro studies of isoxazole derivatives as potent antioxidant and antibacterial agents synthesized via one-pot methodology. Res Chem Intermed. 2023;49(3):859-83. doi: 10.1007/s11164-022-04910-7. [Google Scholar] [Crossref]

16. Eid AM, Hawash M, Amer J, Jarrar A, Qadri S, Alnimer I, et al. Synthesis and biological evaluation of novel isoxazole-amide analogues as anticancer and antioxidant agents. BioMed Res Int. 2021;2021:6633297. doi: 10.1155/2021/6633297, PMID 33763478. [Google Scholar] [Crossref]

17. Saleem A, Farooq U, Bukhari SM, Khan S, Zaidi A, Wani TA, et al. Isoxazole derivatives against carbonic anhydrase: synthesis, molecular docking, MD simulations, and free energy calculations coupled with in vitro studies. ACS Omega. 2022;7(34): 30359-30368. doi: 10.1021/acsomega.2c03600, PMID 36061660. [Google Scholar] [Crossref]

18. Bulanov, Denis DA., et al Novokshonova IA, Novokshonov VV, Ushakov IA, Sterkhova IV.”Facile one-pot synthesis of 5–substituted isoxazoles and pyrazoles through microwave-promoted intramolecular cyclization of y-hydroxyalkynal oximes and hydrozones.”. Synthetic Communication 47.4. (2017);47(4): 335-343. doi;10.1080/00397911.2016.1263892. [Google Scholar] [Crossref]

19. Sagar, P., et al. "Synthesis & Evaluation of isoxazole for their antimicrobial activity.". Int. J. Comp. Adv. Pharmacol 2. (2017);2: 19-26. [Google Scholar] [Crossref]

20. Breijyeh, Zeinab, and Rafik Karaman R. "Design and Ssynthesis of Nnovel Aantimicrobial Aagents.". Antibiotics (Basel) 12.3. (2023);12(3): 628. doi: 10.3390/antibiotics12030628, PMID 36978495. [Google Scholar] [Crossref]

21. Mohatt, Jessica JL., et al., Hu L, Finneran KT, Strathmann TJ. "Microbially mediated abiotic transformation of the antimicrobial agent sulfamethoxazole under iron-reducing soil conditions.". Environmental sScience & tTechnology 45.11. (2011);45(11): 4793-4801. doi: 10.1021/es200413g, PMID 21542626. [Google Scholar] [Crossref]

22. Hawash, Mohammed, Jaradat N, Abualhasan M, Qaoud MT, Joudeh Y, Jaber Z, et al. "Molecular docking studies and biological evaluation of isoxazole-carboxamide derivatives as COX inhibitors and antimicrobial agents.". 3 Biotech 12.12. (2022);12(12): 342. doi: 10.1007/s13205-022-03408-8, PMID 36345437. [Google Scholar] [Crossref]

23. Kalirajan, R., et al. "Synthesis and biological evaluation of some heterocyclic derivatives of chalcones.". International J. of Chem Technol Research 1.1. (2009);1(1): 27-34. [Google Scholar] [Crossref]

24. Patoliya, Pareshkumar PU., et al. "Synthesis and biological evaluation of some new chalcone and isoxazole derivatives.". The International Journal of Science and Technoledge 2.5. (2014);2(5): 138. [Google Scholar] [Crossref]

25. The International Journal of Science and Technoledge 2.5 (2014): 138.Patoliya, Pareshkumar PU., et al. "Synthesis and biological evaluation of some new chalcone and isoxazole derivatives.". The Int J Sci Technoledge. 2014;2(5):138. [Google Scholar] [Crossref]

26. Dabhi, A. R., A. K. Rana AK, and A. R. Shah AR. "Synthesis, characterization and biological evaluation of some novel isoxazole and benzodiazepine derivatives.". Journal of Chemical and Pharmaceutical Research 6.11. (2014);6(11): 771-775. [Google Scholar] [Crossref]

27. Agrawal, Bhagyashree, Bhaskar Kumar Gupta BK, and Satish Kumar Sahu SK. "Synthesis, Characterization and Biological Evaluation of some new Iisoxazole and Ppyrazole compounds for Anti-obesity drug.". Research Journal of Pharmacy and Technology 16.8. (2023);16(8): 3837-3842. [Google Scholar] [Crossref]

28. Zimecki, Michał, Urszula Bąchor U, and Marcin Mączyński M. "Isoxazole derivatives as regulators of immune functions.". Molecules 23.10. (2018);23(10): 2724. doi: 10.3390/molecules23102724, PMID 30360408. [Google Scholar] [Crossref]

29. Çalışkan, Burcu, et al., Sinoplu E, İbiş K, Akhan Güzelcan E, Çetin Atalay R, Banoglu E. "Synthesis and cellular bioactivities of novel isoxazole derivatives incorporating an arylpiperazine moiety as anticancer agents.". Journal of enzyme inhibition and medicinal chemistry 33.1. (2018);33(1): 1352-1361. doi: 10.1080/14756366.2018.1504041, PMID 30251900. [Google Scholar] [Crossref]

30. Shaik Khadar Yazdan*, Kambhampati Uma Rani, Kunta Sindhura (2014 May 1). Synthesis of Substituted Isoxazole Derivatives from Chalcones and their Antibacterial Activity. PHARMANEST,5(2),1991-1994. http://www.pharmanest.net. [Google Scholar] [Crossref]

31. Hussain, Zameer, et al. "Theoretical study of isoxazoles and their derivatives for evaluating its pharmaceutical properties with density functional theory.". J Comput Chem Mol Model 4.3. (2020);4(3): 415-426. [Google Scholar] [Crossref]

32. Loh, Belinda, Vozzolo L, Mok BJ, Lee CC, Fitzmaurice RJ, Caddick S, et al. "Inhibition of HIV‐-1 Rreplication by Iisoxazolidine and Iisoxazole Ssulfonamides.". Chemical Biology & Drug Design 75.5. (2010);75(5): 461-474. doi: 10.1111/j.1747-0285.2010.00956.x, PMID 20486932. [Google Scholar] [Crossref]

33. Panda, Krishna ChandraKC, Bera Venkata Varaha Ravi Kumar BeraVV, and Biswa Mohan Sahoo BM. "’Microwave-Assisted Facile Synthesis and In vitro Anti-microbial Activities of Some Novel Isoxazole Derivatives via Chalcones."’ NVEO-NATURAL VOLATILES & ESSENTIAL OILS Journal| NVEO (2021): 11503-11510. [Google Scholar] [Crossref]

34. Dou, Guolan, et al., Xu P, Li Q, Xi Y, Huang Z, Shi D. "Clean and efficient synthesis of isoxazole derivatives in aqueous media.". mMolecules 18.11. (2013);18(11): 13645-13653. doi: 10.3390/molecules181113645, PMID 24196411. [Google Scholar] [Crossref]

35. Aksöz, B. Evranos, and Rahmiye Ertan. "Chemical and structural properties of chalcones I." Fabad J Pharm Sci 36. (2011);36: 223-242. [Google Scholar] [Crossref]

36. Jin, Ruifa, Weidong Sun W, and Shanshan Tang S. "A DFT study of pyrrole-isoxazole derivatives as chemosensors for fluoride anion.". International Journal of Molecular Sciences 13.9. (2012);13(9): 10986-10999. doi: 10.3390/ijms130910986, PMID 23109833. [Google Scholar] [Crossref]

37. Cha, Minjun, et al., Baek S, Lee W, Shin K, Lee JW. "Tuning behaviors of methane inclusion in isoxazole clathrate hydrates.". Journal of Chemical & Engineering Data 60.2. (2015);60(2): 278-283. doi: 10.1021/je500568f. [Google Scholar] [Crossref]

38. Gehling, Victor VS., Hewitt MC, Vaswani RG, Leblanc Y, Côté A, Nasveschuk CG, et al. "Discovery, design, and optimization of isoxazole azepine BET inhibitors.". ACS mMedicinal cChemistry lLetters 4.9. (2013);4(9): 835-840. doi: 10.1021/ml4001485, PMID 24900758. [Google Scholar] [Crossref]

39. Waldo, Jesse JP., and Richard C. Larock RC. "Synthesis of isoxazoles via electrophilic cyclization.". Organic lLetters 7.23. (2005);7(23): 5203-5205. doi: 10.1021/ol052027z, PMID 16268538. [Google Scholar] [Crossref]

40. Gutiérrez, Margarita, et al., Amigo J, Fuentes E, Palomo I, Astudillo L. "Synthetic isoxazole as antiplatelet agent.". Platelets 25.4. (2014);25(4): 234-238. doi: 10.3109/09537104.2013.807335, PMID 23841686. [Google Scholar] [Crossref]

41. Galenko, Ekaterina EE., et al., Linnik SA, Khoroshilova OV, Novikov MS, Khlebnikov AF. "Isoxazole strategy for the synthesis of α-aminopyrrole derivatives.". The Journal of Organic Chemistry 84.17. (2019);84(17): 11275-11285. doi: 10.1021/acs.joc.9b01634, PMID 31385507 [Google Scholar] [Crossref]

Metrics

Views & Downloads

Similar Articles