International Journal of Drug Delivery Technology
Volume 14, Issue 2

Synthesis, Pharmacological Study of 3,5-Di- Substituted Isoxazole Derivatives as Anticancer Drug Against Breast Cancer Cell Line Followed by Computational Study

Sonali Waghmare*, Ramesh Sawant

Dr. VithalraoVikhe Patil Foundation’s College of Pharmacy, Ahmednagar, Affiliated to Savitribai Phule Pune University,Pune, Maharashtra, India.

Received: 26th March, 2023; Revised: 10th May, 2024; Accepted: 19th May, 2024; Available Online: 25th June, 2024 

ABSTRACT

Objective: Cancer has remained a challenge to the healthcare system due to changes in eating habits and lifestyle, tremendous side effects of chemotherapy, and resistance to existing treatment due to mutations, which creates difficulty in identifying specific targets.

Chemistry and Methodology: In this study, equimolecular amounts of reagents were used to synthesize substituted isoxazoles from alpha-beta unsaturated intermediates.

Result: Compounds were collected in varying amounts of yield. Spectroscopic data supports the formation of compounds.

Compound Id shows GI50 of 46.3 μg/mL against MDA-MB-231.

Conclusion: The effective synthesis of novel derivatives has opened up exciting new avenues for medicinal research; one of

these compounds has moderate anticancer properties.

Keywords: Heterocycles, Isoxazole, Anticancer activity.

International Journal of Drug Delivery Technology (2024); DOI: 10.25258/ijddt.14.2.67

How to cite this article: Waghmare S, Sawant R. Synthesis, Pharmacological Study of 3,5-Di- Substituted Isoxazole Derivatives as Anticancer Drug Against Breast Cancer Cell Line Followed by Computational Study. International Journal of Drug Delivery Technology. 2024;14(2):1051-1054.

REFERENCES

  1. Aronov M, Structure-Guided Design of Potent and Selective Pyrimidylpyrrole Inhibitors of Extracellular Signal-Regulated Kinase (ERK) Using Conformational Control. Journal of Medicinal Chemistry.2009;52:62-68. Available from: doi.org/ 1021/jm900630q
  2. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F. Global cancer observatory: cancer today. Lyon, France: international agency for research on 2018 Nov 5;3(20):2019. Available from: doi.org/10.1002/ijc.33588.
  3. Sheikh Antimicrobial, Antioxidant, and Anticancer Activities of Some Novel Isoxazole Ring Containing Chalcone and Dihydropyrazole Derivatives. Molecules. 2020;25:1047. Available from: doi.org/ 10.3390/molecules25051047
  4. Arya GC, Kaur K, Jaitak V. Isoxazole derivatives as anticancer agent: A review on synthetic strategies, mechanism of action and SAR studies. European Journal of Medicinal 2021;221:113511. Available from: doi.org/ 10.1016/j. ejmech.2021.113511
  5. Agrawal N, Mishra The synthetic and therapeutic expedition of isoxazole and its analogues. Medicinal Chemistry Research. 2018;27:1309–1344. Available from: doi.org/ 10.1007/s00044- 018-2152-6
  6. Pfeiffer RM, Webb-Vargas Y, Wheeler W, Gail Proportion of US trends in breast cancer incidence attributable to long- term changes in risk factor distributions. Cancer Epidemiology Biomarkers and Prevention. 2018;27:1214-1222. Available from: doi.org/ 10.1158/1055-9965.EPI-18-0098
  7. Kalirajan R, Murlidharan V, Jubie S, Sankar S. Microwave assisted synthesis, characterization and evaluation for their antimicrobial activities of some novel pyrazole substituted 9-anilino acridine derivatives. International Journal of Health Allied Science . 2013;2:81-87.
  8. Shaintaf H.A. Green synthesis of chalcone under microwave irradiation. International Journal of Chemical Technology Research. 2016; 2:36-39. Available from https://sphinxsai. com/2016/ch_vol9_no2/1/(36-39)V9N2CT.pdf
  9. Bhalgat M, Patil S, Chitale S, Randive K, Patil K, Patil S. Synthesis and Cytotoxic Studies of Newer 3-(1-Benzofuran- 2-Yl)-5- (Substituted Aryl) Isoxazole. Research Journal of Pharmacy and Technology. 2011; 4: 247-251. Available from https://rjptonline.org/HTMLPaper.aspx?Journal=Research+Jo urnal+of+Pharmacy+and+Technology%3bPID%3d2011-4-2-6
  10. Zu hongtian, Lei T, Zang C, Wei B, Yang Synthesis of chalcone derivatives: inducing apoptosis of Hep G2 cells via regulating reactive oxygen species and mitochondrial pathway. Frontiers in pharmacology. 2019;10: 1-13. Available from: 10.3389/ fphar.2019.01341
  11. Sevim, R. Sila K, Bedia K, Suna. Synthesis and evaluation of cytotoxic activities of some substituted isoxazolone Marmara Pharmaceutical Journal. Available from: 2011;15:94-99. Avialble from: doi.org/10.12991/MPJ.62173
  12. Mosawi S, Hazam H, Abbas A. Microwave Assisted Synthesis, Characterizationand Biological Studyof Some Heterocyclic Derived from Chalcone Research Journal of Pharmaceutical, Biological and Chemical sciences.2019;103:117-128. Available from doi.org/ 10.7176/CMR/11-3-05
  13. Jadhav N, Rajput S, Patel S.Chaudhari S, microwave assisted solvent free synthesis and evaluation of antimicrobial and antioxidant activities of some novel 3, 4-bis (substituted phenyl)- 7-(6-methyl pyridin-2-yl)-3, 3a, 3b, 4-tetrahydro-7h-pyrrolo [2, 3-c : 5,4 c’] di isoxazole. Journal of advanced scientific research. 2022;13:112-119. Available from: doi.org/ 10.55218/ 202213513
  14. YadzaniS, Rani K, Sindhura K, Synthesis of Substituted isoxazole Derivatives from Chalcones and Their Antibacterial Activity). International Journal of Advances in Pharmaceutical Sciences. 2014; 5:1991-1994. Available from: https:// academia.edu/7001072/synthesis_of_substituted_isoxazole_ derivatives_from_chalcones_and_their_antibacterial_activity
  15. Panda K, Varaha V, Kumar R. and Sahoo B. Microwave irradiated green synthesis of novel isoxazole derivatives as anti-epileptic agent. Current Trends in Biotechnology and 2022;16: 25-30. Available from: doi.org/ 10.5530/ctbp.2022.3s.59
  16. Saxena S, Szabo CI, Chopin S, Barjhoux L, Sinilnikova O, Lenoir G, Goldgar DE, Bhatanager D. BRCA1 and BRCA2 in Indian breast cancer patients. Human Mutation. 2002;20:473–474. Available from: doi.org/ 10.1002/humu.9082.
  17. VanichaVichai and Sulforhodamine B colorimetric assay for cytotoxicity screening Nature Protocols 2006; 1: 1112–1116. Available from: doi.org/ 10.1038/ nprot.2006.179.
  18. Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, ; Vistica, D.; Warren, J.T.; Bokesch, H.; Kenney, S.; Boyd,M.R. New colorimetric cytotoxicity assay for anticancer-drug screening. Journal of National Cancer Institute. 1990; 82: 1107- 1112. Available from: doi.org/ 10.1093/jnci/82.13.1107.
  19. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor Journal of Computational Chemistry. 2009;30:2785–2791. Available from: doi.org/ 10.1002/jcc.21256
  20. Liaoa Q, Gaoa Q, Weia J, and Chou K; Docking and Molecular Dynamics Study on the Inhibitory Activity of Novel Inhibitors on Epidermal Growth Factor Receptor (EGFR). Medicinal Chemistry.2011;7:24-31. Available from: doi.org/ 2174/157340611794072698.
  21. Somaia S. Abd El-Karim, Manal M. Anwar, Neama A. Mohamed, Tamer Nasr, Samia A. Elseginy Design, synthesis, biological evaluation and molecular docking studies of novel benzofuran- pyrazole derivatives as anticancer agent’s bioorganic 20215;63,1-12. Available from: doi.org/ 10.1016/j. bioorg.2015.08.006.
  22. Deore S, Wagh V, Tare H, Kayande N, Thube U. Molecular Docking Analysis of Potentilla fulgens Polyphenols against Estrogen Receptors Involved in Breast Cancer. International Journal of Pharmaceutical Quality 2024;15:346- 350. Available from: doi.org/ 10.25258/ijpqa.15.1.55
  23. Tare H, Vaidya V, Fulmali S, Jadhao S, Wankhade M, Bhise Transcriptomic Insight and Structural Integration: Repositioning FDA-Approved Methotrexate Derivative for Precision Therapy in Lung Cancer through Drug-Drug Similarity Analysis and Cavity-Guided Blind Docking. International Research Journal of Multidisciplinary Scope. 2024;5:631-639. Available from: doi. org/ 10.47857/irjms.2024.v05i01.0300
  24. Deore S, Wagh V, Thorat M, Bidkar S, Tare In-silico Discovery of Potential Dengue Type 2 Virus NS1 Inhibitors: A Natural Ligand Zingerone-Derived 3-Point Pharmacophore Screening and Structure-Guided Blind Docking Study. International Journal of Pharmaceutical Quality Assurance. 2024;15:414-16