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Year 2024, Volume: 28 Issue: 6, 1901 - 1910, 28.06.2025

Sevgi Karakuş , Fatih Tok , Burçin İrem Abas , Elif Tütüncü Nigar Kübra Kalkan Sevda Türk , Özge Çevik

https://doi.org/10.29228/jrp.863

Abstract

References

  • [1] Kashyap D, Pal D, Sharma R, Garg VK, Goel N, Koundal D, Zaguia A, Koundal S, Belay A. Global Increase in Breast Cancer Incidence: Risk Factors and Preventive Measures. Biomed Res Int. 2022; 2022: 9605439. https://doi.org/10.1155/2022/9605439.
  • [2] World Health Organization (WHO). International Agency for Research on Cancer (IARC). Cancer Tomorrow. Globocan 2022 (version 1.1). https://gco.iarc.who.int. (accessed on 20 July 2024).
  • [3] McDonald ES, Clark AS, Tchou J, Zhang P, Freedman GM. Clinical Diagnosis and Management of Breast Cancer. J Nucl Med. 2016; 57: 9S-16S. https://doi.org/10.2967/jnumed.115.157834.
  • [4] Akram M, Iqbal M, Daniyal M, Khan AU. Awareness and current knowledge of breast cancer. Biol Res. 2017; 50(1): 1-23. https://doi.org/10.1186/s40659-017-0140-9.
  • [5] Tommasi C, Balsano R, Corianò M, Pellegrino B, Saba G, Bardanzellu F, Denaro N, Ramundo M, Toma I, Fusaro A, Martella S, Aiello MM, Scartozzi M, Musolino A, Solinas C. Long-term effects of breast cancer therapy and care: calm after the storm? J Clin Med. 2022; 11(23): 1-17. https://doi.org/10.3390/jcm11237239
  • [6] Çakmak R, Başaran E, Şahin K, Şentürk M, Durdağı S. Synthesis of novel hydrazide–hydrazone compounds and ın vitro and ın silico ınvestigation of their biological activities against AChE, BChE, and hCA I and II. ACS Omega. 2024;9(18): 20030–20041. https://doi.org/10.1021/acsomega.3c10182
  • [7] Tok F, Çelikçi T, Acar AB, Baltaş N, Başoğlu F, Karakuş S. Synthesis, in-vitro inhibition of cholinesterase and in silico studies of new hydrazide-hydrazones derived from Clopidogrel. J Mol Struct. 2024; 1314: 138763. https://doi.org/10.1016/j.molstruc.2024.138763
  • [8] Tok F, Sağlık BN, Özkay Y, Kaplancıklı ZA, Koçyiğit-Kaymakçıoğlu B. Design, synthesis, biological activity evaluation and in silico studies of new nicotinohydrazide derivatives as multi-targeted inhibitors for Alzheimer's disease. J Mol Struct. 2022; 1265: 133441. https://doi.org/10.1016/j.molstruc.2022.133441
  • [9] Tok F, Sağlık BN, Özkay Y, Kaplancıklı ZA, Koçyiğit-Kaymakçıoğlu B. N-substituted arylidene-3-(methylsulfonyl) 2-oxoimidazolidine-1-carbohydrazide as cholinesterase ınhibitors: Design, synthesis, and molecular docking study. Chem Biodivers. 2022; 19(8): e202200265. https://doi.org/10.1002/cbdv.202200265
  • [10] Akdağ K, Ünal G, Tok F, Arıcıoğlu F, Temel HE, Koçyiğit-Kaymakçıoğlu B. Synthesis and biological evaluation of some new hydrazone derivatives bearing pyrimidine ring as analgesic and anti-inflammatory agents. Acta Pol Pharm. 2018; 75(5): 1147-1159. https://doi.org/10.32383/appdr/86743
  • [11] Murugappan S, Dastari S, Jungare K, Barve NM, Shankaraiah N. Hydrazide-hydrazone/hydrazone as enabling linkers in anti-cancer drug discovery: A comprehensive review. J Mol Struct. 2024; 1307: 138012. https://doi.org/10.1016/j.molstruc.2024.138012 [12] Acar Çevik U, Sağlık BN, Ardıç CM, Özkay Y, Atlı Ö. Synthesis and evaluation of new benzimidazole derivatives with hydrazone moiety as anticancer agents. Turk J Biochem. 2018; 43(2): 2018, 151 158. https://doi.org/10.1515/tjb-2017-0167
  • [13] Osmaniye D, Levent S, Karaduman AB, Ilgın S, Özkay Y, Kaplancıklı ZA. Synthesis of new benzothiazole acylhydrazones as anticancer agents. Molecules. 2018; 23(5): 1054. https://doi.org/10.3390/molecules23051054
  • [14] Akdağ K, Tok F, Karakuş S, Erdoğan Ö, Çevik Ö, Koçyiğit-Kaymakçıoğlu B. Synthesis and biological evaluation of some hydrazide-hydrazone derivatives as anticancer agents. Acta Chim Slov. 2022; 69: 863-875. https://doi.org/10.17344/acsi.2022.7614
  • [15] Saral Çakmak S, Erdoğan Ö, Başoğlu F, Çoruh U, Çevik Ö, Karakuş S. Exploring etofenamate hydrazide hydrazone/copper(II) complexes: Synthesis, anticancer activity, carbonic anhydrase IX inhibition and docking studies. J Mol Struct. 2024; 1312: 138555. https://doi.org/10.1016/j.molstruc.2024.138555
  • [16] Koçyiğit-Kaymakçıoğlu B, Yazıcı SS, Tok F, Dikmen M, Engür S, Oruç Emre EE, İyidoğan A. Synthesis and anticancer activity of new hydrazide-hydrazones and their Pd(II) complexes. Lett Drug Des Discov. 2019; 16(5): 522 532. https://doi.org/10.2174/1570180815666180816124102
  • [17] Li Y, Wang H, Oosterwijk E, Tu C, Shiverick KT, Silverman DN, Frost SC. Expression and activity of carbonic anhydrase IX ıs associated with metabolic dysfunction in MDA-MB-231 breast cancer cells. Cancer Invest. 2009; 27(6): 613–623. https://doi.org/10.1080/07357900802653464
  • [18] Potter C, Harris AL. Hypoxia inducible carbonic anhydrase IX, marker of tumour hypoxia, survival pathway and therapy target. Cell Cycle. 2004; 3(2): 164-167.
  • [19] Simko V, Takacova M, Debreova M, Laposova K, Ondriskova-Panisova E, Pastorekova S, Csaderova L and Pastorek J. Dexamethasone downregulates expression of carbonic anhydrase IX via HIF-1α and NF-κB-dependent mechanisms. Int J Oncol. 2016; 49: 1277-1288. https://doi.org/10.3892/ijo.2016.362

Synthesis and in vitro anticancer activity of some new hydrazide-hydrazones derived from articaine

Year 2024, Volume: 28 Issue: 6, 1901 - 1910, 28.06.2025

Sevgi Karakuş , Fatih Tok , Burçin İrem Abas , Elif Tütüncü Nigar Kübra Kalkan Sevda Türk , Özge Çevik

https://doi.org/10.29228/jrp.863

Abstract

In this study, synthesis of some new hydrazone derivatives based on articaine was carried out. MDA-MB 231 (triple negative human breast cancer cells) and HUVEC (human umbilical vein endothelial cells) cells were used to investigate the cytotoxic activity of hydrazone compounds. Induction of apoptosis and cell viability were assessed by AnnexinV-PI binding levels and Bax-Bcl2 gene expression levels. Inhibitory activities of the compounds against carbonic anhydrase enzyme were also evaluated. Compounds 2b and 2m exhibited the highest cytotoxic activity against MDA MB-231 cells with IC50 values of 16.62±1.18 µM and 18.56±2.36 µM, respectively. Similarly, the CA inhibition of 2b and 2m was also determined to be the highest in the series.

Keywords

Hydrazone Articaine breast cancer carbonic anhydrase bax

References

  • [1] Kashyap D, Pal D, Sharma R, Garg VK, Goel N, Koundal D, Zaguia A, Koundal S, Belay A. Global Increase in Breast Cancer Incidence: Risk Factors and Preventive Measures. Biomed Res Int. 2022; 2022: 9605439. https://doi.org/10.1155/2022/9605439.
  • [2] World Health Organization (WHO). International Agency for Research on Cancer (IARC). Cancer Tomorrow. Globocan 2022 (version 1.1). https://gco.iarc.who.int. (accessed on 20 July 2024).
  • [3] McDonald ES, Clark AS, Tchou J, Zhang P, Freedman GM. Clinical Diagnosis and Management of Breast Cancer. J Nucl Med. 2016; 57: 9S-16S. https://doi.org/10.2967/jnumed.115.157834.
  • [4] Akram M, Iqbal M, Daniyal M, Khan AU. Awareness and current knowledge of breast cancer. Biol Res. 2017; 50(1): 1-23. https://doi.org/10.1186/s40659-017-0140-9.
  • [5] Tommasi C, Balsano R, Corianò M, Pellegrino B, Saba G, Bardanzellu F, Denaro N, Ramundo M, Toma I, Fusaro A, Martella S, Aiello MM, Scartozzi M, Musolino A, Solinas C. Long-term effects of breast cancer therapy and care: calm after the storm? J Clin Med. 2022; 11(23): 1-17. https://doi.org/10.3390/jcm11237239
  • [6] Çakmak R, Başaran E, Şahin K, Şentürk M, Durdağı S. Synthesis of novel hydrazide–hydrazone compounds and ın vitro and ın silico ınvestigation of their biological activities against AChE, BChE, and hCA I and II. ACS Omega. 2024;9(18): 20030–20041. https://doi.org/10.1021/acsomega.3c10182
  • [7] Tok F, Çelikçi T, Acar AB, Baltaş N, Başoğlu F, Karakuş S. Synthesis, in-vitro inhibition of cholinesterase and in silico studies of new hydrazide-hydrazones derived from Clopidogrel. J Mol Struct. 2024; 1314: 138763. https://doi.org/10.1016/j.molstruc.2024.138763
  • [8] Tok F, Sağlık BN, Özkay Y, Kaplancıklı ZA, Koçyiğit-Kaymakçıoğlu B. Design, synthesis, biological activity evaluation and in silico studies of new nicotinohydrazide derivatives as multi-targeted inhibitors for Alzheimer's disease. J Mol Struct. 2022; 1265: 133441. https://doi.org/10.1016/j.molstruc.2022.133441
  • [9] Tok F, Sağlık BN, Özkay Y, Kaplancıklı ZA, Koçyiğit-Kaymakçıoğlu B. N-substituted arylidene-3-(methylsulfonyl) 2-oxoimidazolidine-1-carbohydrazide as cholinesterase ınhibitors: Design, synthesis, and molecular docking study. Chem Biodivers. 2022; 19(8): e202200265. https://doi.org/10.1002/cbdv.202200265
  • [10] Akdağ K, Ünal G, Tok F, Arıcıoğlu F, Temel HE, Koçyiğit-Kaymakçıoğlu B. Synthesis and biological evaluation of some new hydrazone derivatives bearing pyrimidine ring as analgesic and anti-inflammatory agents. Acta Pol Pharm. 2018; 75(5): 1147-1159. https://doi.org/10.32383/appdr/86743
  • [11] Murugappan S, Dastari S, Jungare K, Barve NM, Shankaraiah N. Hydrazide-hydrazone/hydrazone as enabling linkers in anti-cancer drug discovery: A comprehensive review. J Mol Struct. 2024; 1307: 138012. https://doi.org/10.1016/j.molstruc.2024.138012 [12] Acar Çevik U, Sağlık BN, Ardıç CM, Özkay Y, Atlı Ö. Synthesis and evaluation of new benzimidazole derivatives with hydrazone moiety as anticancer agents. Turk J Biochem. 2018; 43(2): 2018, 151 158. https://doi.org/10.1515/tjb-2017-0167
  • [13] Osmaniye D, Levent S, Karaduman AB, Ilgın S, Özkay Y, Kaplancıklı ZA. Synthesis of new benzothiazole acylhydrazones as anticancer agents. Molecules. 2018; 23(5): 1054. https://doi.org/10.3390/molecules23051054
  • [14] Akdağ K, Tok F, Karakuş S, Erdoğan Ö, Çevik Ö, Koçyiğit-Kaymakçıoğlu B. Synthesis and biological evaluation of some hydrazide-hydrazone derivatives as anticancer agents. Acta Chim Slov. 2022; 69: 863-875. https://doi.org/10.17344/acsi.2022.7614
  • [15] Saral Çakmak S, Erdoğan Ö, Başoğlu F, Çoruh U, Çevik Ö, Karakuş S. Exploring etofenamate hydrazide hydrazone/copper(II) complexes: Synthesis, anticancer activity, carbonic anhydrase IX inhibition and docking studies. J Mol Struct. 2024; 1312: 138555. https://doi.org/10.1016/j.molstruc.2024.138555
  • [16] Koçyiğit-Kaymakçıoğlu B, Yazıcı SS, Tok F, Dikmen M, Engür S, Oruç Emre EE, İyidoğan A. Synthesis and anticancer activity of new hydrazide-hydrazones and their Pd(II) complexes. Lett Drug Des Discov. 2019; 16(5): 522 532. https://doi.org/10.2174/1570180815666180816124102
  • [17] Li Y, Wang H, Oosterwijk E, Tu C, Shiverick KT, Silverman DN, Frost SC. Expression and activity of carbonic anhydrase IX ıs associated with metabolic dysfunction in MDA-MB-231 breast cancer cells. Cancer Invest. 2009; 27(6): 613–623. https://doi.org/10.1080/07357900802653464
  • [18] Potter C, Harris AL. Hypoxia inducible carbonic anhydrase IX, marker of tumour hypoxia, survival pathway and therapy target. Cell Cycle. 2004; 3(2): 164-167.
  • [19] Simko V, Takacova M, Debreova M, Laposova K, Ondriskova-Panisova E, Pastorekova S, Csaderova L and Pastorek J. Dexamethasone downregulates expression of carbonic anhydrase IX via HIF-1α and NF-κB-dependent mechanisms. Int J Oncol. 2016; 49: 1277-1288. https://doi.org/10.3892/ijo.2016.362
There are 18 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Chemistry
Journal Section Articles
Authors

Sevgi Karakuş 0000-0002-7911-8372

Fatih Tok 0000-0002-4569-008X

Burçin İrem Abas 0000-0002-1018-5577

Elif Tütüncü 0009-0007-5155-0271

Nigar Kübra Kalkan 0009-0003-0744-4069

Sevda Türk 0000-0002-4567-6739

Özge Çevik

Publication Date June 28, 2025
Submission Date August 2, 2024
Acceptance Date September 1, 2024
Published in Issue Year 2024 Volume: 28 Issue: 6

Cite

APA Karakuş, S., Tok, F., Abas, B. İ., Tütüncü, E., et al. (2025). Synthesis and in vitro anticancer activity of some new hydrazide-hydrazones derived from articaine. Journal of Research in Pharmacy, 28(6), 1901-1910. https://doi.org/10.29228/jrp.863
AMA Karakuş S, Tok F, Abas Bİ, Tütüncü E, Kalkan NK, Türk S, Çevik Ö. Synthesis and in vitro anticancer activity of some new hydrazide-hydrazones derived from articaine. J. Res. Pharm. July 2025;28(6):1901-1910. doi:10.29228/jrp.863
Chicago Karakuş, Sevgi, Fatih Tok, Burçin İrem Abas, Elif Tütüncü, Nigar Kübra Kalkan, Sevda Türk, and Özge Çevik. “Synthesis and in Vitro Anticancer Activity of Some New Hydrazide-Hydrazones Derived from Articaine”. Journal of Research in Pharmacy 28, no. 6 (July 2025): 1901-10. https://doi.org/10.29228/jrp.863.
EndNote Karakuş S, Tok F, Abas Bİ, Tütüncü E, Kalkan NK, Türk S, Çevik Ö (July 1, 2025) Synthesis and in vitro anticancer activity of some new hydrazide-hydrazones derived from articaine. Journal of Research in Pharmacy 28 6 1901–1910.
IEEE S. Karakuş, F. Tok, B. İ. Abas, E. Tütüncü, N. K. Kalkan, S. Türk, and Ö. Çevik, “Synthesis and in vitro anticancer activity of some new hydrazide-hydrazones derived from articaine”, J. Res. Pharm., vol. 28, no. 6, pp. 1901–1910, 2025, doi: 10.29228/jrp.863.
ISNAD Karakuş, Sevgi et al. “Synthesis and in Vitro Anticancer Activity of Some New Hydrazide-Hydrazones Derived from Articaine”. Journal of Research in Pharmacy 28/6 (July 2025), 1901-1910. https://doi.org/10.29228/jrp.863.
JAMA Karakuş S, Tok F, Abas Bİ, Tütüncü E, Kalkan NK, Türk S, Çevik Ö. Synthesis and in vitro anticancer activity of some new hydrazide-hydrazones derived from articaine. J. Res. Pharm. 2025;28:1901–1910.
MLA Karakuş, Sevgi et al. “Synthesis and in Vitro Anticancer Activity of Some New Hydrazide-Hydrazones Derived from Articaine”. Journal of Research in Pharmacy, vol. 28, no. 6, 2025, pp. 1901-10, doi:10.29228/jrp.863.
Vancouver Karakuş S, Tok F, Abas Bİ, Tütüncü E, Kalkan NK, Türk S, Çevik Ö. Synthesis and in vitro anticancer activity of some new hydrazide-hydrazones derived from articaine. J. Res. Pharm. 2025;28(6):1901-10.