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Vol. 36 No. 3 (2024): Vol 36 Issue 3, 2024

Copyright (c) 2024 S. Ugrappa, D. Jagadeesan, P. Lalitha, M. Ravichandran, M. Solyappan, G.H. Khor, Y.S. Wu, V. Balakrishnan, D. Thangeswaran, S. Fuloria

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Synthesis, Characterization, Docking Studies and in vitro Response of New Camptothecin Derivatives towards Oral Squamous Cell Carcinoma

https://doi.org/10.14233/ajchem.2024.31038
S. Ugrappa
Department of Biotechnology, Faculty of Applied Sciences, AIMST University, Kedah 08100, Malaysia
https://orcid.org/0000-0002-0369-2642
D. Jagadeesan
Department of Biotechnology, Faculty of Applied Sciences, AIMST University, Kedah 08100, Malaysia
https://orcid.org/0009-0006-4254-0840
P. Lalitha
Department of Biochemistry, Faculty of Medicine, AIMST University, Bedong 08100, Kedah, Malaysia
https://orcid.org/0009-0003-9319-4675
M. Ravichandran
Department of Biotechnology, Faculty of Applied Sciences, AIMST University, Kedah 08100, Malaysia
https://orcid.org/0000-0001-5321-1344
M. Solyappan
Department of Biotechnology, Faculty of Applied Sciences, AIMST University, Kedah 08100, Malaysia
https://orcid.org/0000-0002-2629-4583
G.H. Khor
Centre of Preclinical Science Studies, Faculty of Dentistry, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia Oral and Maxillofacial Cancer Research Group. Faculty of Dentistry, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia
https://orcid.org/0000-0002-4686-7668
Y.S. Wu
School of Medical and Life Sciences, Sunway University, Subang Jaya 47500, Selangor, Malaysia
https://orcid.org/0000-0001-5574-8049
V. Balakrishnan
Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800 Pulau Pinang, Malaysia
https://orcid.org/0000-0002-4874-600X
D. Thangeswaran
Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800 Pulau Pinang, Malaysia
https://orcid.org/0000-0001-8715-0383
S. Fuloria
Faculty of Pharmacy, AIMST University, Bedong 08100, Kedah, Malaysia
https://orcid.org/0000-0002-5381-5655

Corresponding Author(s) : S. Ugrappa

srideviugrappa@gmail.com

Asian Journal of Chemistry, Vol. 36 No. 3 (2024): Vol 36 Issue 3, 2024

Abstract

Evidence suggests heterocyclic rings as the essential component of various available chemotherapeutics. Present study was aimed to carry out the molecular docking, synthesis, characterization and response of new camptothecin derivatives (NCDs) towards OSCC cell lines. To achieve the aim of the study, new camptothecin derivatives were designed to perform molecular docking against the target protein Human DNA Topoisomerase-1 (1T8I). Molecules 2 and 3 with high docking scores were subjected to synthesis. In current investigation, NCDs were synthesized by cyclization of imino analogue (2) into a new azetidinone derivative (3) on treatment with triethylamine and chloroacetyl chloride. Synthesized NCDs were characterized using IR, NMR and mass analysis. The NCDs were further subjected to antiproliferation study using CAL-27 (OSCC), followed by in vitro DNA relaxation assay and cell cycle analysis. The results of the docking of CPT-11 against Human DNA Topoisomerase-1 Duplex (PDB ID: 1T8I) in present study revealed compound 2 and 3 exhibited high docking score among all camptothecin analogues. Present study successfully synthesized and elucidated the structures of NCD 2 and 3. The antiproliferation study results revealed that NCD 2 and NCD 3 offered an IC50 of 34.73 µg/mL and 62.5 µg/mL, respectively. The DNA relaxation assay exhibited the inhibition action of synthesized NCDs (IC50 concentration) against topoisomerase enzyme. Moreover, the cell cycle analysis revealed that both NCDs arrested cancer cells in ‘S’ phase. Though the present study highlights the potential of NCDs against oral squamous cell carcinoma, however, the present study also recommends that the synthesized NCDs must be further evaluated for preclinical and clinical significance.

Keywords

Azetidinone Characterization Irinotecan Imine Synthesis
Ugrappa, S., Jagadeesan, D., Lalitha, P., Ravichandran, M., Solyappan, M., Khor, G., … Fuloria, S. (2024). Synthesis, Characterization, Docking Studies and in vitro Response of New Camptothecin Derivatives towards Oral Squamous Cell Carcinoma. Asian Journal of Chemistry, 36(3), 731–739. https://doi.org/10.14233/ajchem.2024.31038
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References
  1. M. Ramesh, P. Ahlawat and N.R. Srinivas, Biomed. Chromatogr., 24, 104 (2010); https://doi.org/10.1002/bmc.1345
  2. S. Warnakulasuriya, H. Maeda and J.S. Greenspan, Pathology of Oral and Oropharyngeal Cancers, In: Textbook of Oral Cancer: Prevention, Diagnosis and Management, Springer, Cham. pp. 69–80 (2020); https://doi.org/10.1007/978-3-030-32316-5_7
  3. H. Sung, J. Ferlay, R.L. Siegel, M. Laversanne, I. Soerjomataram, A. Jemal and F. Bray, CA Cancer J. Clin., 71, 209 (2021); https://doi.org/10.3322/caac.21660
  4. A. Sofi-Mahmudi, M. Masinaei, E. Shamsoddin, M.R. Tovani-Palone, M.-H. Heydari, S. Shoaee, E. Ghasemi, S. Azadnajafabad, S. Roshani, N. Rezaei, M.-M. Rashidi, R.K. Mehrjardi, A.A. Hajebi, B. Larijani and F. Farzadfar, BMC Oral Health, 21, 558 (2021); https://doi.org/10.1186/s12903-021-01918-0
  5. S. Furness, A.M. Glenny, H.V. Worthington, K.K. Chan S. Pavitt, R. Oliver, J.E. Clarkson, M. Macluskey and D.I. Conway, Cochrane Database Syst. Rev., 4, CD006386 (2011); https://doi.org/10.1002/14651858.CD006386.pub2
  6. M.I. Bellantoni, G. Picciolo, I. Pirrotta, N. Irrera, M. Vaccaro, F. Vaccaro, F. Squadrito and G. Pallio, Biomedicines, 11, 1112 (2023); https://doi.org/10.3390/biomedicines11041112
  7. S.D. da Silva, M. Hier, A. Mlynarek, L.P. Kowalski and M.A. Alaoui-Jamali, Front. Pharmacol., 3, 149 (2012); https://doi.org/10.3389/fphar.2012.00149
  8. Z.N. Lei, Q. Tian, Q.X. Teng, J.N. Wurpel, L. Zeng, Y. Pan and Z.S. Chen, MedComm, 4, e265 (2023); https://doi.org/10.1002/mco2.265
  9. M. Kciuk, B. Marciniak and R. Kontek, Int. J. Mol. Sci., 21, 4919 (2020); https://doi.org/10.3390/ijms21144919
  10. L.Y. Bai, M.H. Yang, N.J. Chiang, S.Y. Wu, C.Y. Lin, M.Y. Lien, J.H. Chen, M.H. Chang, C.Y. Hsieh, R.L. Hong, H.F. Kao, R.-H. Ye, S.-H. Chen, C.-F. Hsiao, L.-T. Chen and T.-W. Liu, J. Clin. Oncol., 39(15Suppl), 6025 (2021); https://doi.org/10.1200/JCO.2021.39.15_suppl.6025
  11. F. Chen, H. Wang, J. Zhu, R. Zhao, P. Xue, Q. Zhang, M. Bud Nelson, W. Qu, B. Feng and J. Pi, Br. J. Cancer, 117, 1495 (2017); https://doi.org/10.1038/bjc.2017.317
  12. D.S. Salunkhe and P.B. Piste, Int. J. Pharm. Life Sci., 5, 1 (2014).
  13. S.H. Alotabi, Arab. J. Chem., 13, 4771 (2020); https://doi.org/10.1016/j.arabjc.2019.12.006
  14. A.T. McNutt, P. Francoeur, R. Aggarwal, T. Masuda, R. Meli, M. Ragoza, J. Sunseri and D.R. Koes, J. Cheminform., 13, 43 (2021); https://doi.org/10.1186/s13321-021-00522-2
  15. A.D. Hunter, J. Chem. Educ., 74, 905 (1997); https://doi.org/10.1021/ed074p905
  16. N.M. O’Boyle, M. Banck, C.A. James, C. Morley, T. Vandermeersch and G.R. Hutchison, J. Cheminform., 3, 33 (2011); https://doi.org/10.1186/1758-2946-3-33
  17. Z.M. Alamshany, R.R. Khattab, N.A. Hassan, A.A. El-Sayed, M.A. Tantawy, A. Mostafa and A.A. Hassan, Molecules, 28, 739 (2023); https://doi.org/10.3390/molecules28020739
  18. P. Bhardwaj, G.P. Biswas, N. Mahata, S. Ghanta and B. Bhunia, Chemosphere, 293, 133550 (2022); https://doi.org/10.1016/j.chemosphere.2022.133550
  19. M.A. Sa’ad, R. Kavitha, S. Fuloria, N.K. Fuloria, M. Ravichandran and P. Lalitha, Antibiotics, 11, 207 (2022); https://doi.org/10.3390/antibiotics11020207
  20. A.A. Abu-Yamin, M.S. Abduh, S.A.M. Saghir and N. Al-Gabri, Pharmaceuticals, 15, 454 (2022); https://doi.org/10.3390/ph15040454
  21. L.R. Venkataravanappa, M. Jyothi, H.A. Khamees, E. Silina, V. Stupin, R.R. Achar, M. Al-Ghorbani and S.A. Khanum, Curr. Issues Mol. Biol., 45, 92 (2022); https://doi.org/10.3390/cimb45010007
  22. D. Aziz, M.M. Majeed and A.T. Salim, J. Popul. Ther. Clin. Pharmacol., 30, e349 (2023); https://doi.org/10.47750/jptcp.2023.30.07.041
  23. C. Huang, H. Zhang, Y. Yang, H. Liu, J. Chen, Y. Wang, L. Liang, H. Hu and Y. Liu, J. Inorg. Biochem., 247, 112329 (2023); https://doi.org/10.1016/j.jinorgbio.2023.112329
  24. K. Govindarao, N. Srinivasan, R. Suresh, R.K. Raheja, S. Annadurai, R.R. Bhandare and A.B. Shaik, J. Saudi Chem. Soc., 26, 101471 (2022); https://doi.org/10.1016/j.jscs.2022.101471
  25. A. Talukdar, B. Kundu, D. Sarkar, S. Goon and M.A. Mondal, Eur. J. Med. Chem., 236, 114304 (2022); https://doi.org/10.1016/j.ejmech.2022.114304
  26. A. Ligasová, I. Frydrych and K. Koberna, Int. J. Mol. Sci., 24, 3674 (2023); https://doi.org/10.3390/ijms24043674
  27. F. Madeddu, J. Di Martino, M. Pieroni, D. Del Buono, P. Bottoni, L. Botta, T. Castrignanò and R. Saladino, Int. J. Mol. Sci., 23, 14652 (2022); https://doi.org/10.3390/ijms232314652
  28. M. Li, L. Wang, Y. Wei, W. Wang, Z. Liu, A. Zuo, W. Liu, J. Tian and H. Wang, Pharmaceuticals, 16, 53 (2022); https://doi.org/10.3390/ph16010053
  29. P.A. Yakkala, N.R. Penumallu, S. Shafi and A. Kamal, Pharmaceuticals, 16, 1456 (2023); https://doi.org/10.3390/ph16101456
  30. Z.-F. Zeng, Q.-P. Huang, J.-H. Cai, G.-J. Zheng, Q.-C. Huang, Z.-L. Liu, Z.-L. Chen and Y.-H. Wei, Molecules, 26, 4028 (2021); https://doi.org/10.3390/molecules26134028
  31. Y. Li, D. Zhao, W. Zhang, M. Yang, Z. Wu, W. Shi, S. Lan, Z. Guo, H. Yu and D. Wu, J. Transl. Med., 21, 422 (2023); https://doi.org/10.1186/s12967-023-04196-2
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