Issue

Vol. 37 No. 5 (2025): Vol 37 Issue 5, 2025

Copyright (c) 2025 Aruna Jyothi Chatla, Nagaraju Dharavath, Praveen Mamidala, Poorna Chandar Gugulothu, Jayaprakash Rao Yerrabelly

Creative Commons License

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

Synthesis, Anticancer and EGFR Inhibitory Activity of Novel [1,2,4]Triazolo[3,4-b][1,3,4]thiadiazine-isoxazoles

https://doi.org/10.14233/ajchem.2025.33420
Aruna Jyothi Chatla
Department of Chemistry, Telangana University, Nizamabad-503322, India
https://orcid.org/0009-0005-7129-5795
Nagaraju Dharavath
Department of Chemistry, Telangana University, Nizamabad-503322, India
https://orcid.org/0009-0002-8163-3397
Praveen Mamidala
Department of Biotechnology, Telangana University, Nizamabad-503322, India
https://orcid.org/0000-0001-8587-0635
Poorna Chandar Gugulothu
Department of Life Sciences, Central University Tamilnadu, Thiruvarur-610005, India
https://orcid.org/0000-0001-7185-9507
Jayaprakash Rao Yerrabelly
Department of Chemistry, Telangana University, Nizamabad-503322, India; Department of Chemistry, Osmania University, Hyderabad-500007, India
https://orcid.org/0000-0003-4387-8334

Corresponding Author(s) : Jayaprakash Rao Yerrabelly

yjpr_19@yahoo.com

Asian Journal of Chemistry, Vol. 37 No. 5 (2025): Vol 37 Issue 5, 2025

Abstract

A novel approach was utilized for the synthesis of new [1,2,4]triazolo[3,4-b] [1,3,4]thiadiazine containing isoxazoles (6a-o) from 3-ethynyl-6-(4-fluorophenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine-8,8-dioxide (4) in combination with freshly prepared substituted nitrile oxides (5) using Cu(I)-catalyzed [3+2] cycloaddition method. The in vitro cancer activity of the synthesized compounds was carried out against two lung cancer cell lines, A-549 and H1299. Among the compounds tested, 6h, 6k and 6l exhibited significantly stronger anticancer activity compared to standard drug erlotinib, with IC50 values ranging from 0.62 ± 0.20 to 4.40 ± 0.14 µM. The cytotoxicity of the more potent compounds was also tested against HEK-293 normal cell line and showed no toxic activity. Compound 6k appears to have higher inhibitory activity against EGFR (IC50 = 0.41 ± 0.03 µM) compared to the standard drug erlotinib (IC50 = 0.42 ± 0.03 µM), while compounds 6h and 6l demonstrated prominent activity. Further potent molecule believed to be a future drug for lung cancer.

Keywords

Anticancer activity EGFR Isoxazole [1,3,4]Thiadiazine [1,2,4]Triazole
(1)
Chatla, A. J.; Dharavath, N.; Mamidala, P.; Gugulothu, P. C.; Yerrabelly, J. R. Synthesis, Anticancer and EGFR Inhibitory Activity of Novel [1,2,4]Triazolo[3,4-b][1,3,4]thiadiazine-Isoxazoles. ajc 2025, 37, 1237-1245.
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. K.P. Rakesh, H.K. Kumara, H.M. Manukumar and D.C. Gowda, Bioorg. Chem., 87, 252 (2019); https://doi.org/10.1016/j.bioorg.2019.03.038
  2. B. Moku, L. Ravindar, K. Rakesh and H.-L.J.B. Qin, Bioorg. Chem., 86, 513 (2019); https://doi.org/10.1016/j.bioorg.2019.02.030
  3. F. Nasim, B.F. Sabath and G.A. Eapen, Med. Clin. North Am., 103, 463 (2019); https://doi.org/10.1016/j.mcna.2018.12.006
  4. B. Majem, E. Nadal and C. Muñoz-Pinedo, Semin. Cell Dev. Biol., 98, 54 (2020); https://doi.org/10.1016/j.semcdb.2019.06.004
  5. M. Salehi, A. Movahedpour, A. Tayarani, Z. Shabaninejad, H. Khan, M.H. Pourhanifeh, E. Mortezapour, A. Nickdasti, R. Mottaghi, A. Davoodabadi, A. Savardashtaki and H. Mirzaei, Phytother. Res., 34, 2557 (2020); https://doi.org/10.1002/ptr.6704.
  6. Y. Zhang, X. Meng, H. Tang, M. Cheng, F. Yang and W. Xu, J. Enzyme Inhib. Med. Chem., 35, 344 (2020); https://doi.org/10.1080/14756366.2019.1702653
  7. M.E. Gray, J. Meehan, P. Sullivan, J.R.K. Marland, S.N. Greenhalgh, R. Gregson, R.E. Clutton, C. Ward, C. Cousens, D.J. Griffiths, A. Murray and D. Argyle, Front. Oncol., 9, e335 (2019); https://doi.org/10.3389/fonc.2019.00335
  8. M. Coakley and S. Popat, Medicine, 48, 273 (2020); https://doi.org/10.1016/j.mpmed.2020.01.003
  9. T. Holbro and N.E. Hynes, Annu. Rev. Pharmacol. Toxicol., 44, 195 (2004); https://doi.org/10.1146/annurev.pharmtox.44.101802.121440
  10. Y. Yarden and M.X. Sliwkowski, Nat. Rev. Mol. Cell Biol., 2, 127 (2001); https://doi.org/10.1038/35052073
  11. X.H. Ma, R. Wang, C.Y. Tan, Y.Y. Jiang, T. Lu, H.B. Rao, X.Y. Li, M.L. Go, B.C. Low and Y.Z. Chen, Mol. Pharm., 7, 1545 (2010); https://doi.org/10.1021/mp100179t
  12. D.H. Boschelli, Drugs Future, 24, 515 (1999); https://doi.org/10.1358/dof.1999.024.05.858622
  13. P.L. Zhao, A.N. Duan, M. Zou, H.K. Yang, W.W. You and S.G. Wu, Bioorg. Med. Chem. Lett., 22, 4471 (2012); https://doi.org/10.1016/j.bmcl.2012.03.023
  14. A. Husain, M. Rashid, M. Shaharyar, A.A. Siddiqui and R. Mishra, Eur. J. Med. Chem., 62, 785 (2013); https://doi.org/10.1016/j.ejmech.2012.07.011
  15. Z. Liu, B. Lang, M. Gao, X. Chang, Q. Guan, Q. Xu, D. Wu, Z. Li, D. Zuo, W. Zhang and Y. Wu, J. Cell. Biochem., 121, 2184 (2020); https://doi.org/10.1002/jcb.29442
  16. B. Zhang, Y.H. Li, Y. Liu, Y.R. Chen, E.S. Pan, W.W. You and P.L. Zhao, Eur. J. Med. Chem., 103, 335 (2015); https://doi.org/10.1016/j.ejmech.2015.08.053
  17. A. Ibrar, S. Zaib, F. Jabeen, J. Iqbal and A. Saeed, Arch. Pharm., 349, 553 (2016); https://doi.org/10.1002/ardp.201500392
  18. P. Telukuntla, M. Chandrakanth, P.G. Amrutha, N.M. Thomas, R. Gondru, K.R. Valluru and J. Banothu, Tetrahedron Lett., 146, 155180 (2024); https://doi.org/10.1016/j.tetlet.2024.155180
  19. G.C. Arya, K. Kaur and V. Jaitak, Eur. J. Med. Chem., 221, 113511 (2021); https://doi.org/10.1016/j.ejmech.2021.113511
  20. E. Rajanarendar, K.G. Reddy, S. Ramakrishna, M.N. Reddy, B. Shireesha, G. Durgaiah and Y.N. Reddy, Bioorg. Med. Chem. Lett., 22, 6677 (2012); https://doi.org/10.1016/j.bmcl.2012.08.098
  21. E.T. Warda, I.A. Shehata, M.B. El-Ashmawy and N.S. El-Gohary, Bioorg. Med. Chem., 28, 115674 (2020); https://doi.org/10.1016/j.bmc.2020.115674
  22. J. Yong, C. Lu and X. Wu, Lett. Drug Des. Discov., 15, 463 (2018); https://doi.org/10.2174/1570180814666170530093549
  23. D. Im, K. Jung, S. Yang, W. Aman and J. Hah, Eur. J. Med. Chem., 102, 600 (2015); https://doi.org/10.1016/j.ejmech.2015.08.031
  24. S. Johnpasha, R. Palabindela, M. Azam, R. Kapavarapu, V. Nasipireddy, S.I. Al-Resayes and S. Narsimha, J. Mol. Struct., 1312, 138440 (2024); https://doi.org/10.1016/j.molstruc.2024.138440
  25. S.R. Bandi, N. Kavitha, S.K. Nukala, N.S. Thirukovela, R. Manchal, R. Palabindela and S. Narsimha, J. Mol. Struct., 1274, 134378 (2023); https://doi.org/10.1016/j.molstruc.2022.134378
  26. R. Samala, R.K. M, A.K. Bapuram, V. Nasipireddy and S. Narsimha, J. Heterocycl. Chem., 61, 600 (2024); https://doi.org/10.1002/jhet.4788
  27. S. Narsimha, S.K. Nukala, T.S. Jyostna, M. Ravinder, M.S. Rao and N.V. Reddy, J. Heterocycl. Chem., 57, 1655 (2020); https://doi.org/10.1002/jhet.3890
  28. S.R. Bandi, R. Kapavarapu, R. Palabindela, M. Azam, K. Min and S. Narsimha, J. Mol. Struct., 1294, 136451 (2023); https://doi.org/10.1016/j.molstruc.2023.136451
  29. N. Dharavath, R. Eligeti, Y.N. Reddy, P.K. Pittala and N.R. Modugu, ChemistrySelect, 2, 5110 (2017); https://doi.org/10.1002/slct.201700640
  30. S.R. Krishna, D. Nagaraju, M.S. Reddy and E. Rajanarendar, J. Heterocycl. Chem., 59, 1341 (2022); https://doi.org/10.1002/jhet.4473
  31. R. Saini, S.R. Malladi and N. Dharavath, J. Heterocycl. Chem., 55, 1579 (2018); https://doi.org/10.1002/jhet.3191
  32. N. Deepavath, A.J. Chatla, V. Kummari, J.R. Yerrabelly, N. Dharavath and R.K. Saini, J. Mol. Struct., 1325, 141033 (2025); https://doi.org/10.1016/j.molstruc.2024.141033
  33. T.V. Hansen, P. Wu and V.V. Fokin, J. Org. Chem., 70, 7761 (2005); https://doi.org/10.1021/jo050163b
  34. S. Chirra, R. Gondru, M. Manne, M. Azam, S.I. Al-Resayes, R. Manchal and S. Narsimha, J. Mol. Struct., 1306, 137803 (2024); https://doi.org/10.1016/j.molstruc.2024.137803
Read More
Author biographies is not available.
Crossref
Scopus
Google Scholar
Europe PMC
Download
PDF
Statistic
Read Counter : 155 Download : 146
PlumX