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In Vitro Assessment of Antiproliferative Properties of a Novel Benzoxazole-Conjugated Pyrrolotriazinone

Yıl 2025, Cilt: 9 Sayı: 1, 107 - 116

Burak Kuzu , Kemal Alp Nalcı

https://doi.org/10.32571/ijct.1564244

Öz

In this study, a new class of antiproliferative agents was designed and synthesized against glioblastoma, the most lethal and aggressive primary brain tumor. The structure was designed by hybridizing benzoxazole and pyrrolotriazinone, two important pharmacophore groups for antiproliferation. The target compound was synthesized in a six-step procedure. The structure of the benzoxazole-conjugated pyrrolotriazinone compound was characterized by FT-IR, 1H- and 13C-NMR spectra. It was found to have favorable drug similarity and theoretical pharmacokinetic parameters according to in silico methods. The antiproliferative effect of the target compound on the glioblastoma cell line U-87 MG was evaluated, showing dose-dependent effectiveness. Furthermore, this study investigates the molecular docking of the novel compound with key glioblastoma-associated targets, revealing its potential as a multi-target therapeutic agent. The compound demonstrates strong binding affinity and inhibitory potential against VEGFR-2, VEGFR-1, and PI3K, and shows significant activity in apoptotic pathways through Caspase-3 and BCL-2. These results suggest its potential to disrupt tumor growth, angiogenesis, and cell proliferation. Overall, the benzoxazole-conjugated pyrrolotriazinone hybrid structure shows promise for glioblastoma treatment and could represent a significant step forward in the design of new drug candidates in the future.

Anahtar Kelimeler

Antiproliferation Benzoxazole Druglikeness Glioblastoma Pyrrolotriazinone

Kaynakça

  • 1. Bisoyi, P. A brief tour guide to cancer disease. Understanding Cancer; Jain, B., Pandey S., Eds.; Academic Press: 2022, pp 1-20.
  • 2. Zeeshan, R.; Mutahir, Z. Bosnian J. Basic Med. Sci. 2017, 17(3), 172-182.
  • 3. Kari, S.; Subramanian, K.; Altomonte, I. A.; Murugesan, A.; Yli-Harja, O.; Kandhavelu, M. Apoptosis 2022, 27 (7), 482–508.
  • 4. Morana, O.; Wood, W.; Gregory, C. D. Int. J. Mol. Sci. 2022, 23 (3), 1328.
  • 5. Quail, D. F.; Joyce, J. A. Nat. Med. 2013, 19 (11), 1423–1437.
  • 6. Guo, X.; Song, J.; Liu, M.; Ou, X.; Guo, Y. Cancer Biol. Ther. 2024, 25 (1), 2356831.
  • 7. Wang, X.; Zhang, H.; Chen, X. Cancer Drug Resist. 2019, 2 (2), 141.
  • 8. Anand, U.; Dey, A.; Chandel, A. K. S.; Sanyal, R.; Mishra, A.; Pandey, D. K.; de la Lastra, J. M. P. Genes Dis. 2023, 10 (4), 1367–1401.
  • 9. Lah, T. T.; Novak, M.; Breznik, B. In Seminars in Cancer Biology; Academic Press: 2020; Vol. 60, pp 262–273.
  • 10. D’Alessio, A.; Proietti, G.; Sica, G.; Scicchitano, B. M. Cancers 2019, 11 (4), 469.
  • 11. Wang, D.; Wang, C.; Wang, L.; Chen, Y. Drug Deliv. 2019, 26 (1), 551–565.
  • 12. Noch, E. K.; Ramakrishna, R.; Magge, R. World Neurosurg. 2018, 116, 505–517.
  • 13. Singh, S.; Utreja, D.; Kumar, V. Med. Chem. Res. 2022, 1–25.
  • 14. Kuzu, B.; Acikgoz, E.; Cakir, M. J. Mol. Struct. 2024, 1309, 138199.
  • 15. Kuzu, B.; Hepokur, C.; Alagoz, M. A.; Burmaoglu, S.; Algul, O. ChemistrySelect 2022, 7 (1), e202103559.
  • 16. Kuzu, B.; Hepokur, C.; Turkmenoglu, B.; Burmaoglu, S.; Algul, O. Future Med. Chem. 2022, 14 (14), 1027–1048.
  • 17. Amărandi, R. M.; Al-Matarneh, M. C.; Popovici, L.; Ciobanu, C. I.; Neamțu, A.; Mangalagiu, I. I.; Danac, R. Pharmaceuticals 2023, 16 (6), 865.
  • 18. Ge, T.; Cintrat, J. C. Pharmaceuticals 2021, 14 (12), 1275.
  • 19. Kuzu, E.; Kuzu, B. Chem. Heterocycl. Compd. 2023, 59 (1), 80–87.
  • 20. Jia, H.; Dai, G.; Su, W.; Xiao, K.; Weng, J.; Zhang, Z.; Bembenek, S. D. J. Med. Chem. 2019, 62 (10), 4936–4948.
  • 21. Carrera Carrera, F.; Perez Garcia, J. B.; Vidal Juan, B.; Sanchez Izquierdo, F.; Serra Coma, M. C. WO Patent WO2015181052 A, 2015.
  • 22. Sicak, Y. Turk. J. Chem. 2022, 46 (3), 665-676.
  • 23. Özgür, G. K.; Dervişoğlu, G.; Özdemir, F. A.; Özdemir, N.; Şerbetçi, Z.; Dayan, O. Appl. Organomet. Chem. 2024, 38 (2), e7342.
  • 24. Çelik, Ş.; Dervişoğlu, G.; İzol, E.; Sęczyk, Ł.; Özdemir, F. A.; Yilmaz, M. E.; Khan, M. A. . Biomed. Chromatogr. 2024, e5975.
  • 25. Thornton, A. M.; Humphrey, R. M.; Kerr, D. M.; Finn, D. P.; Roche, M. Molecules 2021, 26 (12), 3720.
  • 26. Kuzu, B.; Arzuk, E. Chem. Biodiversity 2024, e202401673.
  • 27. Sıcak, Y.; Başaran, E.; Türkmenoğlu, B.; Öztürk, M. J. Mol. Struct. 2025, 140417.

Yıl 2025, Cilt: 9 Sayı: 1, 107 - 116

Burak Kuzu , Kemal Alp Nalcı

https://doi.org/10.32571/ijct.1564244

Öz

Kaynakça

  • 1. Bisoyi, P. A brief tour guide to cancer disease. Understanding Cancer; Jain, B., Pandey S., Eds.; Academic Press: 2022, pp 1-20.
  • 2. Zeeshan, R.; Mutahir, Z. Bosnian J. Basic Med. Sci. 2017, 17(3), 172-182.
  • 3. Kari, S.; Subramanian, K.; Altomonte, I. A.; Murugesan, A.; Yli-Harja, O.; Kandhavelu, M. Apoptosis 2022, 27 (7), 482–508.
  • 4. Morana, O.; Wood, W.; Gregory, C. D. Int. J. Mol. Sci. 2022, 23 (3), 1328.
  • 5. Quail, D. F.; Joyce, J. A. Nat. Med. 2013, 19 (11), 1423–1437.
  • 6. Guo, X.; Song, J.; Liu, M.; Ou, X.; Guo, Y. Cancer Biol. Ther. 2024, 25 (1), 2356831.
  • 7. Wang, X.; Zhang, H.; Chen, X. Cancer Drug Resist. 2019, 2 (2), 141.
  • 8. Anand, U.; Dey, A.; Chandel, A. K. S.; Sanyal, R.; Mishra, A.; Pandey, D. K.; de la Lastra, J. M. P. Genes Dis. 2023, 10 (4), 1367–1401.
  • 9. Lah, T. T.; Novak, M.; Breznik, B. In Seminars in Cancer Biology; Academic Press: 2020; Vol. 60, pp 262–273.
  • 10. D’Alessio, A.; Proietti, G.; Sica, G.; Scicchitano, B. M. Cancers 2019, 11 (4), 469.
  • 11. Wang, D.; Wang, C.; Wang, L.; Chen, Y. Drug Deliv. 2019, 26 (1), 551–565.
  • 12. Noch, E. K.; Ramakrishna, R.; Magge, R. World Neurosurg. 2018, 116, 505–517.
  • 13. Singh, S.; Utreja, D.; Kumar, V. Med. Chem. Res. 2022, 1–25.
  • 14. Kuzu, B.; Acikgoz, E.; Cakir, M. J. Mol. Struct. 2024, 1309, 138199.
  • 15. Kuzu, B.; Hepokur, C.; Alagoz, M. A.; Burmaoglu, S.; Algul, O. ChemistrySelect 2022, 7 (1), e202103559.
  • 16. Kuzu, B.; Hepokur, C.; Turkmenoglu, B.; Burmaoglu, S.; Algul, O. Future Med. Chem. 2022, 14 (14), 1027–1048.
  • 17. Amărandi, R. M.; Al-Matarneh, M. C.; Popovici, L.; Ciobanu, C. I.; Neamțu, A.; Mangalagiu, I. I.; Danac, R. Pharmaceuticals 2023, 16 (6), 865.
  • 18. Ge, T.; Cintrat, J. C. Pharmaceuticals 2021, 14 (12), 1275.
  • 19. Kuzu, E.; Kuzu, B. Chem. Heterocycl. Compd. 2023, 59 (1), 80–87.
  • 20. Jia, H.; Dai, G.; Su, W.; Xiao, K.; Weng, J.; Zhang, Z.; Bembenek, S. D. J. Med. Chem. 2019, 62 (10), 4936–4948.
  • 21. Carrera Carrera, F.; Perez Garcia, J. B.; Vidal Juan, B.; Sanchez Izquierdo, F.; Serra Coma, M. C. WO Patent WO2015181052 A, 2015.
  • 22. Sicak, Y. Turk. J. Chem. 2022, 46 (3), 665-676.
  • 23. Özgür, G. K.; Dervişoğlu, G.; Özdemir, F. A.; Özdemir, N.; Şerbetçi, Z.; Dayan, O. Appl. Organomet. Chem. 2024, 38 (2), e7342.
  • 24. Çelik, Ş.; Dervişoğlu, G.; İzol, E.; Sęczyk, Ł.; Özdemir, F. A.; Yilmaz, M. E.; Khan, M. A. . Biomed. Chromatogr. 2024, e5975.
  • 25. Thornton, A. M.; Humphrey, R. M.; Kerr, D. M.; Finn, D. P.; Roche, M. Molecules 2021, 26 (12), 3720.
  • 26. Kuzu, B.; Arzuk, E. Chem. Biodiversity 2024, e202401673.
  • 27. Sıcak, Y.; Başaran, E.; Türkmenoğlu, B.; Öztürk, M. J. Mol. Struct. 2025, 140417.
Toplam 27 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Yapısal Biyoloji , Biyokimya ve Hücre Biyolojisi (Diğer)
Bölüm Makale
Yazarlar

Burak Kuzu 0000-0002-7305-7177

Kemal Alp Nalcı 0000-0003-3786-5246

Erken Görünüm Tarihi 4 Haziran 2025
Yayımlanma Tarihi
Gönderilme Tarihi 10 Ekim 2024
Kabul Tarihi 7 Şubat 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 9 Sayı: 1

Kaynak Göster

APA Kuzu, B., & Nalcı, K. A. (2025). In Vitro Assessment of Antiproliferative Properties of a Novel Benzoxazole-Conjugated Pyrrolotriazinone. International Journal of Chemistry and Technology, 9(1), 107-116. https://doi.org/10.32571/ijct.1564244
AMA Kuzu B, Nalcı KA. In Vitro Assessment of Antiproliferative Properties of a Novel Benzoxazole-Conjugated Pyrrolotriazinone. Int. J. Chem. Technol. Haziran 2025;9(1):107-116. doi:10.32571/ijct.1564244
Chicago Kuzu, Burak, ve Kemal Alp Nalcı. “In Vitro Assessment of Antiproliferative Properties of a Novel Benzoxazole-Conjugated Pyrrolotriazinone”. International Journal of Chemistry and Technology 9, sy. 1 (Haziran 2025): 107-16. https://doi.org/10.32571/ijct.1564244.
EndNote Kuzu B, Nalcı KA (01 Haziran 2025) In Vitro Assessment of Antiproliferative Properties of a Novel Benzoxazole-Conjugated Pyrrolotriazinone. International Journal of Chemistry and Technology 9 1 107–116.
IEEE B. Kuzu ve K. A. Nalcı, “In Vitro Assessment of Antiproliferative Properties of a Novel Benzoxazole-Conjugated Pyrrolotriazinone”, Int. J. Chem. Technol., c. 9, sy. 1, ss. 107–116, 2025, doi: 10.32571/ijct.1564244.
ISNAD Kuzu, Burak - Nalcı, Kemal Alp. “In Vitro Assessment of Antiproliferative Properties of a Novel Benzoxazole-Conjugated Pyrrolotriazinone”. International Journal of Chemistry and Technology 9/1 (Haziran 2025), 107-116. https://doi.org/10.32571/ijct.1564244.
JAMA Kuzu B, Nalcı KA. In Vitro Assessment of Antiproliferative Properties of a Novel Benzoxazole-Conjugated Pyrrolotriazinone. Int. J. Chem. Technol. 2025;9:107–116.
MLA Kuzu, Burak ve Kemal Alp Nalcı. “In Vitro Assessment of Antiproliferative Properties of a Novel Benzoxazole-Conjugated Pyrrolotriazinone”. International Journal of Chemistry and Technology, c. 9, sy. 1, 2025, ss. 107-16, doi:10.32571/ijct.1564244.
Vancouver Kuzu B, Nalcı KA. In Vitro Assessment of Antiproliferative Properties of a Novel Benzoxazole-Conjugated Pyrrolotriazinone. Int. J. Chem. Technol. 2025;9(1):107-16.
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