SYNTHESIS AND CHARACTERIZATION OF NOVEL 5-FLOUROINDOLYLMETHYLEN HYDRAZON DERIVATIVES AS SCHIFF BASE COMPONDS: IN VITRO AND IN SILICO EVALUATION AS POTENTIAL CARBONIC ANHYDRASES (CAI-CAII) INHIBITORS

Cheeghdam Kedik; Nagihan Faydalı; Esra Dilek; Hanif Şirinzade

doi:10.33483/jfpau.1648214

Research Article

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SYNTHESIS AND CHARACTERIZATION OF NOVEL 5-FLOUROINDOLYLMETHYLEN HYDRAZON DERIVATIVES AS SCHIFF BASE COMPONDS: IN VITRO AND IN SILICO EVALUATION AS POTENTIAL CARBONIC ANHYDRASES (CAI-CAII) INHIBITORS

Year 2025, Volume: 49 Issue: 3, 773 - 784, 19.09.2025

Cheeghdam Kedik , Nagihan Faydalı , Esra Dilek , Hanif Şirinzade

https://doi.org/10.33483/jfpau.1648214

Abstract

Objective: In this study, novel 5-fluoroindolylmethylene hydrazone derivatives were synthesized and assessed for their potential inhibitory effects on human carbonic anhydrase I and II (hCA I and II) enzymes through both in vitro and in silico approaches.
Material and Method: Accordingly, starting from 5-fluoroindole, 5-fluoroindole-3-carboxaldehyde was synthesized. The target final compounds were then obtained by condensing substituted phenylhydrazine with 5-fluoroindole-3-carboxaldehyde, resulting in three Schiff base derivatives (2a, 2b, and 2c).
Result and Discussion: The synthesized compounds demonstrated effective inhibition of cytosolic carbonic anhydrase isoforms hCA I and II, with Ki values ranging from 32.28±7.09 to 74.86±10.90 nM for hCA I and 8.79±1.92 to 60.40±14.64 nM for hCA II. Among them, compound 2a exhibited the most potent inhibitory effect on both isoenzymes. In vitro results were verified with the results obtained by docking studies and interactions with enzymes were demonstrated. These novel 5-fluoroindolylmethylene hydrazone derivatives show promise as potent inhibitors of cytosolic CA isoenzymes.

Keywords

5-Flouroindole , carbonic anhydrase , glaucoma , inhibition

Project Number

24202055

References

1. Sandoval, B.A., Hyster, T.K. (2020). Emerging strategies for expanding the toolbox of enzymes in biocatalysis. Current Opinion in Chemical Biology, 55, 45-51. [CrossRef]
2. Ramalho, T.C., de Castro, A.A., Silva, D.R., Silva, M.C., Franca, T.C., Bennion, B.J., Kuca, K. (2016). Computational enzymology and organophosphorus degrading enzymes: Promising approaches toward remediation technologies of warfare agents and pesticides. Current Medicinal Chemistry, 23(10), 1041-1061. [CrossRef]
3. Chen, A.Y., Adamek, R.N., Dick, B.L., Credille, C.V., Morrison, C.N., Cohen, S.M. (2019). Targeting metalloenzymes for therapeutic intervention. Chemical Reviews, 119(2), 1323-1455. [CrossRef]
4. Imtaiyaz Hassan, M., Shajee, B., Waheed, A., Ahmad, F., Sly, W.S. (2013). Structure, function and applications of carbonic anhydrase isozymes. Bioorganic and Medicinal Chemistry, 21(6), 1570-1582. [CrossRef]
5. Supuran, C.T., Vullo, D., Manole, G., Casini, A., Scozzafava, A. (2004). Designing of novel carbonic anhydrase inhibitors and activators. Current Medicinal Chemistry-Cardiovascular and Hematological Agents, 2(1), 49-68. [CrossRef]
6. Supuran, C.T., Scozzafava, A. (2007). Carbonic anhydrases as targets for medicinal chemistry. Bioorganic and Medicinal Chemistry, 15(13), 4336-4350. [CrossRef]
7. Supuran C.T. (2008). Carbonic anhydrases: Novel therapeutic applications for inhibitors and activators. Nature Reviews Drug Discovery, 7(2), 168-181. [CrossRef]
8. Innocenti, A., Vullo, D., Scozzafava, A., Supuran, C.T. (2008). Carbonic anhydrase inhibitors: Interactions of phenols with the 12 catalytically active mammalian isoforms (CA I-XIV). Bioorganic and Medicinal Chemistry Letters, 18(5), 1583-1587. [CrossRef]
9. Oztürk Sarikaya, S.B., Topal, F., Sentürk, M., Gülçin, I., Supuran, C.T. (2011). In vitro inhibition of α-carbonic anhydrase isozymes by some phenolic compounds. Bioorganic and Medicinal Chemistry Letters, 21(14), 4259-4262. [CrossRef]
10. Nair, S.K., Ludwig, P.A., Christianson, D.W. (1994). Two-site binding of phenol in the active site of human carbonic anhydrase II: Structural implications for substrate association. Journal of the American Chemical Society, 116(8), 3659-3660. [CrossRef]
11. Casey, J.R. (2006). Why bicarbonate?. Biochemistry and Cell biology, 84(6), 930-939. [CrossRef]
12. Özbey, F., Taslimi, P., Gülçin, İ., Maraş, A., Göksu, S., Supuran, C.T. (2016). Synthesis of diaryl ethers with acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase inhibitory actions. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(sup2), 79-85. [CrossRef]
13. Garibov, E., Taslimi, P., Sujayev, A., Bingol, Z., Çetinkaya, S., Gulçin, İ., Beydemir, S., Farzaliyev, V., Alwasel, S.H., Supuran, C.T. (2016). Synthesis of 4,5-disubstituted-2-thioxo-1,2,3,4-tetrahydropyrimidines and investigation of their acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase I/II inhibitory and antioxidant activities. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(sup3), 1-9. [CrossRef]
14. Innocenti, A., Hilvo, M., Scozzafava, A., Parkkila, S., Supuran, C.T. (2008). Carbonic anhydrase inhibitors: Inhibition of the new membrane-associated isoform XV with phenols. Bioorganic and Medicinal Chemistry Letters, 18(12), 3593-3596. [CrossRef]
15. Thiry, A., Dogné, J.M., Supuran, C.T., Masereel, B. (2007). Carbonic anhydrase inhibitors as anticonvulsant agents. Current Topics in Medicinal Chemistry, 7(9), 855-864. [CrossRef]
16. Ekinci, D., Beydemir, S., Küfrevioğlu, O.I. (2007). In vitro inhibitory effects of some heavy metals on human erythrocyte carbonic anhydrases. Journal of Enzyme Inhibition and Medicinal Chemistry, 22(6), 745-750. [CrossRef]
17. Supuran C.T. (2008). Diuretics: From classical carbonic anhydrase inhibitors to novel applications of the sulfonamides. Current Pharmaceutical Design, 14(7), 641-648. [CrossRef]
18. Yiğit, B., Yiğit, M., Taslimi, P., Gök, Y., Gülçin, İ. (2018). Schiff bases and their amines: Synthesis and discovery of carbonic anhydrase and acetylcholinesterase enzymes inhibitors. Archiv der Pharmazie, 351(9), e1800146. [CrossRef]
19. Alim Z. (2018). 1H-indazole molecules reduced the activity of human erythrocytes carbonic anhydrase I and II isoenzymes. Journal of Biochemical and Molecular Toxicology, 32(9), e22194. [CrossRef]
20. Taslimi, P., Osmanova, S., Gulçin, İ., Sardarova, S., Farzaliyev, V., Sujayev, A., Kaya, R., Koc, F., Beydemir, S., Alwasel, S.H., Kufrevioglu, O.I. (2017). Discovery of potent carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase enzymes inhibitors: The new amides and thiazolidine-4-ones synthesized on an acetophenone base. Journal of Biochemical and Molecular Toxicology, 31(9), 10. [CrossRef]
21. Aslan, H.E., Demir, Y., Özaslan, M.S., Türkan, F., Beydemir, Ş., Küfrevioğlu, Ö.I. (2019). The behavior of some chalcones on acetylcholinesterase and carbonic anhydrase activity. Drug and Chemical Toxicology, 42(6), 634-640. [CrossRef]
22. Taslimi, P., Sujayev, A., Turkan, F., Garibov, E., Huyut, Z., Farzaliyev, V., Mamedova, S., Gulçin, İ. (2018). Synthesis and investigation of the conversion reactions of pyrimidine-thiones with nucleophilic reagent and evaluation of their acetylcholinesterase, carbonic anhydrase inhibition, and antioxidant activities. Journal of Biochemical and Molecular Toxicology, 32(2), e22019. [CrossRef]
23. Timur, İ., Kocyigit, Ü.M., Dastan, T., Sandal, S., Ceribası, A.O., Taslimi, P., Gulcin, İ., Koparir, M., Karatepe, M., Çiftçi, M. (2018). In vitro cytotoxic and in vivo antitumoral activities of some aminomethyl derivatives of 2,4-dihydro-3H-1,2,4-triazole-3-thiones-Evaluation of their acetylcholinesterase and carbonic anhydrase enzymes inhibition profiles. Journal of Biochemical and Molecular Toxicology, 33, e22239. [CrossRef]
24. Supuran, C.T., Scozzafava, A. (2007). Carbonic anhydrases as targets for medicinal chemistry. Bioorganic and Medicinal Chemistry, 15(13), 4336-4350. [CrossRef]
25. Sly, W.S., Hu, P.Y. (1995). Human carbonic anhydrases and carbonic anhydrase deficiencies. Annual Review of Biochemistry, 64, 375-401. [CrossRef]
26. Ozensoy, O., Arslan, O., Sinan, S.O. (2004). A new method for purification of carbonic anhydrase isozymes by affinity chromatography. Biochemistry, 69(2), 216-219. [CrossRef]
27. Pastorekova, S., Parkkila, S., Pastorek, J., Supuran, C.T. (2004). Carbonic anhydrases: Current state of the art, therapeutic applications and future prospects. Journal of Enzyme Inhibition and Medicinal Chemistry, 19(3), 199-229. [CrossRef]
28. Bayram, E., Senturk, M., Kufrevioglu, O.I., Supuran, C.T. (2008). In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II. Bioorganic and Medicinal Chemistry, 16(20), 9101-9105. [CrossRef]
29. Burmaoğlu, S., Dilek, E., Yılmaz, A.O., Supuran, C.T. (2016). Synthesis of two phloroglucinol derivatives with cinnamyl moieties as inhibitors of the carbonic anhydrase isozymes I and II: An in vitro study. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(2), 208-212. [CrossRef]
30. Caglar, S., Dilek, E., Caglar, B., Adiguzel, E., Temel, E., Buyukgungor, O., Tabak, A. (2016). New metal complexes with diclofenac containing 2-pyridineethanol or 2-pyridinepropanol: synthesis, structural, spectroscopic, thermal properties, catechol oxidase and carbonic anhydrase activities. Journal of Coordination Chemistry, 69(22), 3321-3335. [CrossRef]
31. Suzen, S., Tekiner-Gulbas, B., Shirinzadeh, H., Uslu, D., Gurer-Orhan, H., Gumustas, M., Ozkan, S.A. (2013). Antioxidant activity of indole-based melatonin analogues in erythrocytes and their voltammetric characterization. Journal of Enzyme Inhibition and Medicinal Chemistry, 28(6), 1143-1155. [CrossRef]
32. Shirinzadeh, H., Altanlar, N., Yucel, N., Ozden, S., Suzen, S. (2011). Antimicrobial evaluation of indole-containing hydrazone derivatives. Zeitschrift fur Naturforschung, 66(7-8), 340-344. [CrossRef]
33. Shirinzadeh, H., Neuhaus, E., Ince Erguc, E., Tascioglu Aliyev, A., Gurer-Orhan, H., Suzen, S. (2020). New indole-7-aldehyde derivatives as melatonin analogues; synthesis and screening their antioxidant and anticancer potential. Bioorganic Chemistry, 104, 104219. [CrossRef]
34. Gurer-Orhan, H., Karaaslan, C., Ozcan, S., Firuzi, O., Tavakkoli, M., Saso, L., Suzen, S. (2016). Novel indole-based melatonin analogues: Evaluation of antioxidant activity and protective effect against amyloid β-induced damage. Bioorganic and Medicinal Chemistry, 24(8), 1658-1664. [CrossRef]
35. Purgatorio, R., Gambacorta, N., Catto, M., de Candia, M., Pisani, L., Espargaró, A., Sabaté, R., Cellamare, S., Nicolotti, O., Altomare, C.D. (2020). Pharmacophore modeling and 3D-QSAR study of indole and isatin derivatives as antiamyloidogenic agents targeting Alzheimer's disease. Molecules (Basel, Switzerland), 25(23), 5773. [CrossRef]
36. Heda, L.C., Sharma, R., Chaudhari, P.B. (2009). Viscometric investigations of some derivatives of 5-substituted indole dihydropyrimidines 2-ones in mixed organic solvents. International Journal of Chemical Sciences, 7(3), 1595-1605.
37. Kidwai, M., Negi, N., Gupta, S.D. (1994). Synthesis and antifertility activity of 1,5-diaryl-3-(3'-indolyl)formazans. Chemical and Pharmaceutical Bulletin, 42(11), 2363-2364. [CrossRef]
38. Xiang, F., Xiang, J., Fang, Y., Zhang, M., Li, M. (2014). Discovering isozyme‐selective inhibitor scaffolds of human carbonic anhydrases using structural alignment and de novo drug design approaches. Chemical Biology and Drug Design, 83(2), 247-258. [CrossRef]
39. Huey, R., Morris, G.M. (2008). Using AutoDock 4 with AutoDocktools: A tutorial. The Scripps Research Institute, USA, 8(8), 54-56.
40. Trott, O., Olson, A.J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455-461. [CrossRef]
41. Studio, B.D. (2017). Discovery Studio Visualizer. Biovia Discovery Studio: San Diego, CA, USA, 936.
42. Shirinzadeh, H., Dilek, E. (2020). Synthesis, characterization and biological activity evaluation of novel naphthalenylmethylen hydrazine derivatives as carbonic anhydrase inhibitors. Journal of Molecular Structure, 1220, 128657. [CrossRef]
43. Dilek, E., Caglar, S., Dogancay, N., Caglar, B., Sahin, O., Tabak, A. (2017). Synthesis, crystal structure, spectroscopy, thermal properties and carbonic anhydrase activities of new metal (II) complexes with mefenamic acid and picoline derivatives. Journal of Coordination Chemistry, 70(16), 2833-2852. [CrossRef]
44. Burmaoğlu, S., Dilek, E., Yılmaz, A. O., Supuran, C. T. (2016). Synthesis of two phloroglucinol derivatives with cinnamyl moieties as inhibitors of the carbonic anhydrase isozymes I and II: An in vitro study. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(2), 208-212. [CrossRef]
45. Caglar, S., Dilek, E., Caglar, B., Adiguzel, E., Temel, E., Buyukgungor, O., Tabak, A. (2016). New metal complexes with diclofenac containing 2-pyridineethanol or 2-pyridinepropanol: Synthesis, structural, spectroscopic, thermal properties, catechol oxidase and carbonic anhydrase activities. Journal of Coordination Chemistry, 69(22), 3321-3335. [CrossRef]
46. Bayram, E., Senturk, M., Kufrevioglu, O.I., Supuran, C.T. (2008). In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II. Bioorganic and Medicinal Chemistry, 16(20), 9101-9105. [CrossRef]
47. Bradford, M.M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72(1-2), 248-254. [CrossRef]
48. Verpoorte, J.A., Mehta, S., Edsall, J.T. (1967). Esterase activities of human carbonic anhydrases B and C. Journal of Biological Chemistry, 242(18), 4221-4229. [CrossRef]
49. Supuran, C.T., Scozzafava, A., Casini, A. (2003). Carbonic anhydrase inhibitors. Medicinal Research Reviews, 23(2), 146-189. [CrossRef]
50. Akman, E., Sirinzade, H., Ozguven, S.Y., Dilek, E., Suzen, S. (2024). Enzyme inhibitory potential of some indole Schiff bases on acetylcholinesterase and human carbonic anhydrase isoforms I and II enzymes: An in vitro and molecular docking study. Journal of Biomolecular Structure and Dynamics, 42(22), 12011-12020. [CrossRef]

YENİ 5-FLOROİNDOLİLMETİLEN HİDRAZON TÜREVLERİNİN SCHİFF BAZ BİLEŞİKLERİ OLARAK SENTEZİ VE KARAKTERİZASYONU: POTANSİYEL KARBONİK ANHİDRAZ (CAI-CAII) İNHİBITÖRLERİ OLARAK İN VİTRO VE İN SİLİCO DEĞERLENDİRMESİ

Year 2025, Volume: 49 Issue: 3, 773 - 784, 19.09.2025

Cheeghdam Kedik , Nagihan Faydalı , Esra Dilek , Hanif Şirinzade

https://doi.org/10.33483/jfpau.1648214

Abstract

Amaç: Bu çalışmada, 5-floroindolilmetilen hidrazonun yeni türevleri sentezlendi ve bunların insan karbonik anhidraz I ve II (hCA I ve II) enzimleri üzerindeki potansiyel inhibitör etkileri in vitro ve in silico olarak değerlendirilmesi amaçlandı.
Gereç ve Yöntem: Buna göre, 5-floroindolden başlayarak, 5-floroindol-3-karboksaldehit sentezlendi. Hedef nihai bileşikler daha sonra ikame edilmiş fenilhidrazinin 5-floroindol-3-karboksaldehit ile yoğunlaştırılmasıyla elde edildi ve üç Schiff baz türevi (2a, 2b ve 2c) elde edildi.
Sonuç ve Tartışma: Sentezlenen bileşikler, hCA I için 32.28±7.09 ila 74.86±10.90 nM ve hCA II için 8.79±1.92 ila 60.40±14.64 nM aralığında değişen Ki değerleri ile sitozolik karbonik anhidraz izoformları hCA I ve II'nin etkili inhibisyonunu göstermiştir. Bunlar arasında, bileşik 2a her iki izoenzim üzerinde en güçlü inhibitör etkiyi göstermiştir. İn vitro sonuçlar, yerleştirme çalışmalarıyla elde edilen sonuçlarla doğrulanmış ve enzimlerle etkileşimler gösterilmiştir. Bu yeni 5-floroindolilmetilen hidrazon türevleri, sitozolik CA izoenzimlerinin güçlü inhibitörleri olarak ümit verici görünmektedir.

Keywords

5-Floroindol , glokom , inhibisyon , karbonik anhidraz

Project Number

24202055

References

1. Sandoval, B.A., Hyster, T.K. (2020). Emerging strategies for expanding the toolbox of enzymes in biocatalysis. Current Opinion in Chemical Biology, 55, 45-51. [CrossRef]
2. Ramalho, T.C., de Castro, A.A., Silva, D.R., Silva, M.C., Franca, T.C., Bennion, B.J., Kuca, K. (2016). Computational enzymology and organophosphorus degrading enzymes: Promising approaches toward remediation technologies of warfare agents and pesticides. Current Medicinal Chemistry, 23(10), 1041-1061. [CrossRef]
3. Chen, A.Y., Adamek, R.N., Dick, B.L., Credille, C.V., Morrison, C.N., Cohen, S.M. (2019). Targeting metalloenzymes for therapeutic intervention. Chemical Reviews, 119(2), 1323-1455. [CrossRef]
4. Imtaiyaz Hassan, M., Shajee, B., Waheed, A., Ahmad, F., Sly, W.S. (2013). Structure, function and applications of carbonic anhydrase isozymes. Bioorganic and Medicinal Chemistry, 21(6), 1570-1582. [CrossRef]
5. Supuran, C.T., Vullo, D., Manole, G., Casini, A., Scozzafava, A. (2004). Designing of novel carbonic anhydrase inhibitors and activators. Current Medicinal Chemistry-Cardiovascular and Hematological Agents, 2(1), 49-68. [CrossRef]
6. Supuran, C.T., Scozzafava, A. (2007). Carbonic anhydrases as targets for medicinal chemistry. Bioorganic and Medicinal Chemistry, 15(13), 4336-4350. [CrossRef]
7. Supuran C.T. (2008). Carbonic anhydrases: Novel therapeutic applications for inhibitors and activators. Nature Reviews Drug Discovery, 7(2), 168-181. [CrossRef]
8. Innocenti, A., Vullo, D., Scozzafava, A., Supuran, C.T. (2008). Carbonic anhydrase inhibitors: Interactions of phenols with the 12 catalytically active mammalian isoforms (CA I-XIV). Bioorganic and Medicinal Chemistry Letters, 18(5), 1583-1587. [CrossRef]
9. Oztürk Sarikaya, S.B., Topal, F., Sentürk, M., Gülçin, I., Supuran, C.T. (2011). In vitro inhibition of α-carbonic anhydrase isozymes by some phenolic compounds. Bioorganic and Medicinal Chemistry Letters, 21(14), 4259-4262. [CrossRef]
10. Nair, S.K., Ludwig, P.A., Christianson, D.W. (1994). Two-site binding of phenol in the active site of human carbonic anhydrase II: Structural implications for substrate association. Journal of the American Chemical Society, 116(8), 3659-3660. [CrossRef]
11. Casey, J.R. (2006). Why bicarbonate?. Biochemistry and Cell biology, 84(6), 930-939. [CrossRef]
12. Özbey, F., Taslimi, P., Gülçin, İ., Maraş, A., Göksu, S., Supuran, C.T. (2016). Synthesis of diaryl ethers with acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase inhibitory actions. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(sup2), 79-85. [CrossRef]
13. Garibov, E., Taslimi, P., Sujayev, A., Bingol, Z., Çetinkaya, S., Gulçin, İ., Beydemir, S., Farzaliyev, V., Alwasel, S.H., Supuran, C.T. (2016). Synthesis of 4,5-disubstituted-2-thioxo-1,2,3,4-tetrahydropyrimidines and investigation of their acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase I/II inhibitory and antioxidant activities. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(sup3), 1-9. [CrossRef]
14. Innocenti, A., Hilvo, M., Scozzafava, A., Parkkila, S., Supuran, C.T. (2008). Carbonic anhydrase inhibitors: Inhibition of the new membrane-associated isoform XV with phenols. Bioorganic and Medicinal Chemistry Letters, 18(12), 3593-3596. [CrossRef]
15. Thiry, A., Dogné, J.M., Supuran, C.T., Masereel, B. (2007). Carbonic anhydrase inhibitors as anticonvulsant agents. Current Topics in Medicinal Chemistry, 7(9), 855-864. [CrossRef]
16. Ekinci, D., Beydemir, S., Küfrevioğlu, O.I. (2007). In vitro inhibitory effects of some heavy metals on human erythrocyte carbonic anhydrases. Journal of Enzyme Inhibition and Medicinal Chemistry, 22(6), 745-750. [CrossRef]
17. Supuran C.T. (2008). Diuretics: From classical carbonic anhydrase inhibitors to novel applications of the sulfonamides. Current Pharmaceutical Design, 14(7), 641-648. [CrossRef]
18. Yiğit, B., Yiğit, M., Taslimi, P., Gök, Y., Gülçin, İ. (2018). Schiff bases and their amines: Synthesis and discovery of carbonic anhydrase and acetylcholinesterase enzymes inhibitors. Archiv der Pharmazie, 351(9), e1800146. [CrossRef]
19. Alim Z. (2018). 1H-indazole molecules reduced the activity of human erythrocytes carbonic anhydrase I and II isoenzymes. Journal of Biochemical and Molecular Toxicology, 32(9), e22194. [CrossRef]
20. Taslimi, P., Osmanova, S., Gulçin, İ., Sardarova, S., Farzaliyev, V., Sujayev, A., Kaya, R., Koc, F., Beydemir, S., Alwasel, S.H., Kufrevioglu, O.I. (2017). Discovery of potent carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase enzymes inhibitors: The new amides and thiazolidine-4-ones synthesized on an acetophenone base. Journal of Biochemical and Molecular Toxicology, 31(9), 10. [CrossRef]
21. Aslan, H.E., Demir, Y., Özaslan, M.S., Türkan, F., Beydemir, Ş., Küfrevioğlu, Ö.I. (2019). The behavior of some chalcones on acetylcholinesterase and carbonic anhydrase activity. Drug and Chemical Toxicology, 42(6), 634-640. [CrossRef]
22. Taslimi, P., Sujayev, A., Turkan, F., Garibov, E., Huyut, Z., Farzaliyev, V., Mamedova, S., Gulçin, İ. (2018). Synthesis and investigation of the conversion reactions of pyrimidine-thiones with nucleophilic reagent and evaluation of their acetylcholinesterase, carbonic anhydrase inhibition, and antioxidant activities. Journal of Biochemical and Molecular Toxicology, 32(2), e22019. [CrossRef]
23. Timur, İ., Kocyigit, Ü.M., Dastan, T., Sandal, S., Ceribası, A.O., Taslimi, P., Gulcin, İ., Koparir, M., Karatepe, M., Çiftçi, M. (2018). In vitro cytotoxic and in vivo antitumoral activities of some aminomethyl derivatives of 2,4-dihydro-3H-1,2,4-triazole-3-thiones-Evaluation of their acetylcholinesterase and carbonic anhydrase enzymes inhibition profiles. Journal of Biochemical and Molecular Toxicology, 33, e22239. [CrossRef]
24. Supuran, C.T., Scozzafava, A. (2007). Carbonic anhydrases as targets for medicinal chemistry. Bioorganic and Medicinal Chemistry, 15(13), 4336-4350. [CrossRef]
25. Sly, W.S., Hu, P.Y. (1995). Human carbonic anhydrases and carbonic anhydrase deficiencies. Annual Review of Biochemistry, 64, 375-401. [CrossRef]
26. Ozensoy, O., Arslan, O., Sinan, S.O. (2004). A new method for purification of carbonic anhydrase isozymes by affinity chromatography. Biochemistry, 69(2), 216-219. [CrossRef]
27. Pastorekova, S., Parkkila, S., Pastorek, J., Supuran, C.T. (2004). Carbonic anhydrases: Current state of the art, therapeutic applications and future prospects. Journal of Enzyme Inhibition and Medicinal Chemistry, 19(3), 199-229. [CrossRef]
28. Bayram, E., Senturk, M., Kufrevioglu, O.I., Supuran, C.T. (2008). In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II. Bioorganic and Medicinal Chemistry, 16(20), 9101-9105. [CrossRef]
29. Burmaoğlu, S., Dilek, E., Yılmaz, A.O., Supuran, C.T. (2016). Synthesis of two phloroglucinol derivatives with cinnamyl moieties as inhibitors of the carbonic anhydrase isozymes I and II: An in vitro study. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(2), 208-212. [CrossRef]
30. Caglar, S., Dilek, E., Caglar, B., Adiguzel, E., Temel, E., Buyukgungor, O., Tabak, A. (2016). New metal complexes with diclofenac containing 2-pyridineethanol or 2-pyridinepropanol: synthesis, structural, spectroscopic, thermal properties, catechol oxidase and carbonic anhydrase activities. Journal of Coordination Chemistry, 69(22), 3321-3335. [CrossRef]
31. Suzen, S., Tekiner-Gulbas, B., Shirinzadeh, H., Uslu, D., Gurer-Orhan, H., Gumustas, M., Ozkan, S.A. (2013). Antioxidant activity of indole-based melatonin analogues in erythrocytes and their voltammetric characterization. Journal of Enzyme Inhibition and Medicinal Chemistry, 28(6), 1143-1155. [CrossRef]
32. Shirinzadeh, H., Altanlar, N., Yucel, N., Ozden, S., Suzen, S. (2011). Antimicrobial evaluation of indole-containing hydrazone derivatives. Zeitschrift fur Naturforschung, 66(7-8), 340-344. [CrossRef]
33. Shirinzadeh, H., Neuhaus, E., Ince Erguc, E., Tascioglu Aliyev, A., Gurer-Orhan, H., Suzen, S. (2020). New indole-7-aldehyde derivatives as melatonin analogues; synthesis and screening their antioxidant and anticancer potential. Bioorganic Chemistry, 104, 104219. [CrossRef]
34. Gurer-Orhan, H., Karaaslan, C., Ozcan, S., Firuzi, O., Tavakkoli, M., Saso, L., Suzen, S. (2016). Novel indole-based melatonin analogues: Evaluation of antioxidant activity and protective effect against amyloid β-induced damage. Bioorganic and Medicinal Chemistry, 24(8), 1658-1664. [CrossRef]
35. Purgatorio, R., Gambacorta, N., Catto, M., de Candia, M., Pisani, L., Espargaró, A., Sabaté, R., Cellamare, S., Nicolotti, O., Altomare, C.D. (2020). Pharmacophore modeling and 3D-QSAR study of indole and isatin derivatives as antiamyloidogenic agents targeting Alzheimer's disease. Molecules (Basel, Switzerland), 25(23), 5773. [CrossRef]
36. Heda, L.C., Sharma, R., Chaudhari, P.B. (2009). Viscometric investigations of some derivatives of 5-substituted indole dihydropyrimidines 2-ones in mixed organic solvents. International Journal of Chemical Sciences, 7(3), 1595-1605.
37. Kidwai, M., Negi, N., Gupta, S.D. (1994). Synthesis and antifertility activity of 1,5-diaryl-3-(3'-indolyl)formazans. Chemical and Pharmaceutical Bulletin, 42(11), 2363-2364. [CrossRef]
38. Xiang, F., Xiang, J., Fang, Y., Zhang, M., Li, M. (2014). Discovering isozyme‐selective inhibitor scaffolds of human carbonic anhydrases using structural alignment and de novo drug design approaches. Chemical Biology and Drug Design, 83(2), 247-258. [CrossRef]
39. Huey, R., Morris, G.M. (2008). Using AutoDock 4 with AutoDocktools: A tutorial. The Scripps Research Institute, USA, 8(8), 54-56.
40. Trott, O., Olson, A.J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455-461. [CrossRef]
41. Studio, B.D. (2017). Discovery Studio Visualizer. Biovia Discovery Studio: San Diego, CA, USA, 936.
42. Shirinzadeh, H., Dilek, E. (2020). Synthesis, characterization and biological activity evaluation of novel naphthalenylmethylen hydrazine derivatives as carbonic anhydrase inhibitors. Journal of Molecular Structure, 1220, 128657. [CrossRef]
43. Dilek, E., Caglar, S., Dogancay, N., Caglar, B., Sahin, O., Tabak, A. (2017). Synthesis, crystal structure, spectroscopy, thermal properties and carbonic anhydrase activities of new metal (II) complexes with mefenamic acid and picoline derivatives. Journal of Coordination Chemistry, 70(16), 2833-2852. [CrossRef]
44. Burmaoğlu, S., Dilek, E., Yılmaz, A. O., Supuran, C. T. (2016). Synthesis of two phloroglucinol derivatives with cinnamyl moieties as inhibitors of the carbonic anhydrase isozymes I and II: An in vitro study. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(2), 208-212. [CrossRef]
45. Caglar, S., Dilek, E., Caglar, B., Adiguzel, E., Temel, E., Buyukgungor, O., Tabak, A. (2016). New metal complexes with diclofenac containing 2-pyridineethanol or 2-pyridinepropanol: Synthesis, structural, spectroscopic, thermal properties, catechol oxidase and carbonic anhydrase activities. Journal of Coordination Chemistry, 69(22), 3321-3335. [CrossRef]
46. Bayram, E., Senturk, M., Kufrevioglu, O.I., Supuran, C.T. (2008). In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II. Bioorganic and Medicinal Chemistry, 16(20), 9101-9105. [CrossRef]
47. Bradford, M.M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72(1-2), 248-254. [CrossRef]
48. Verpoorte, J.A., Mehta, S., Edsall, J.T. (1967). Esterase activities of human carbonic anhydrases B and C. Journal of Biological Chemistry, 242(18), 4221-4229. [CrossRef]
49. Supuran, C.T., Scozzafava, A., Casini, A. (2003). Carbonic anhydrase inhibitors. Medicinal Research Reviews, 23(2), 146-189. [CrossRef]
50. Akman, E., Sirinzade, H., Ozguven, S.Y., Dilek, E., Suzen, S. (2024). Enzyme inhibitory potential of some indole Schiff bases on acetylcholinesterase and human carbonic anhydrase isoforms I and II enzymes: An in vitro and molecular docking study. Journal of Biomolecular Structure and Dynamics, 42(22), 12011-12020. [CrossRef]

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Details

Primary Language	English
Subjects	Pharmaceutical Chemistry
Journal Section	Research Article
Authors	Cheeghdam Kedik 0009-0002-4169-3539 Nagihan Faydalı 0000-0002-8895-1825 Esra Dilek 0000-0002-3629-5168 Hanif Şirinzade 0000-0001-9663-9199
Project Number	24202055
Early Pub Date	September 1, 2025
Publication Date	September 19, 2025
Submission Date	February 27, 2025
Acceptance Date	May 5, 2025
Published in Issue	Year 2025 Volume: 49 Issue: 3

Cite

APA	Kedik, C., Faydalı, N., Dilek, E., Şirinzade, H. (2025). SYNTHESIS AND CHARACTERIZATION OF NOVEL 5-FLOUROINDOLYLMETHYLEN HYDRAZON DERIVATIVES AS SCHIFF BASE COMPONDS: IN VITRO AND IN SILICO EVALUATION AS POTENTIAL CARBONIC ANHYDRASES (CAI-CAII) INHIBITORS. Journal of Faculty of Pharmacy of Ankara University, 49(3), 773-784. https://doi.org/10.33483/jfpau.1648214
AMA	Kedik C, Faydalı N, Dilek E, Şirinzade H. SYNTHESIS AND CHARACTERIZATION OF NOVEL 5-FLOUROINDOLYLMETHYLEN HYDRAZON DERIVATIVES AS SCHIFF BASE COMPONDS: IN VITRO AND IN SILICO EVALUATION AS POTENTIAL CARBONIC ANHYDRASES (CAI-CAII) INHIBITORS. J. Fac. Pharm. Ankara. September 2025;49(3):773-784. doi:10.33483/jfpau.1648214
Chicago	Kedik, Cheeghdam, Nagihan Faydalı, Esra Dilek, and Hanif Şirinzade. “SYNTHESIS AND CHARACTERIZATION OF NOVEL 5-FLOUROINDOLYLMETHYLEN HYDRAZON DERIVATIVES AS SCHIFF BASE COMPONDS: IN VITRO AND IN SILICO EVALUATION AS POTENTIAL CARBONIC ANHYDRASES (CAI-CAII) INHIBITORS”. Journal of Faculty of Pharmacy of Ankara University 49, no. 3 (September 2025): 773-84. https://doi.org/10.33483/jfpau.1648214.
EndNote	Kedik C, Faydalı N, Dilek E, Şirinzade H (September 1, 2025) SYNTHESIS AND CHARACTERIZATION OF NOVEL 5-FLOUROINDOLYLMETHYLEN HYDRAZON DERIVATIVES AS SCHIFF BASE COMPONDS: IN VITRO AND IN SILICO EVALUATION AS POTENTIAL CARBONIC ANHYDRASES (CAI-CAII) INHIBITORS. Journal of Faculty of Pharmacy of Ankara University 49 3 773–784.
IEEE	C. Kedik, N. Faydalı, E. Dilek, and H. Şirinzade, “SYNTHESIS AND CHARACTERIZATION OF NOVEL 5-FLOUROINDOLYLMETHYLEN HYDRAZON DERIVATIVES AS SCHIFF BASE COMPONDS: IN VITRO AND IN SILICO EVALUATION AS POTENTIAL CARBONIC ANHYDRASES (CAI-CAII) INHIBITORS”, J. Fac. Pharm. Ankara, vol. 49, no. 3, pp. 773–784, 2025, doi: 10.33483/jfpau.1648214.
ISNAD	Kedik, Cheeghdam et al. “SYNTHESIS AND CHARACTERIZATION OF NOVEL 5-FLOUROINDOLYLMETHYLEN HYDRAZON DERIVATIVES AS SCHIFF BASE COMPONDS: IN VITRO AND IN SILICO EVALUATION AS POTENTIAL CARBONIC ANHYDRASES (CAI-CAII) INHIBITORS”. Journal of Faculty of Pharmacy of Ankara University 49/3 (September2025), 773-784. https://doi.org/10.33483/jfpau.1648214.
JAMA	Kedik C, Faydalı N, Dilek E, Şirinzade H. SYNTHESIS AND CHARACTERIZATION OF NOVEL 5-FLOUROINDOLYLMETHYLEN HYDRAZON DERIVATIVES AS SCHIFF BASE COMPONDS: IN VITRO AND IN SILICO EVALUATION AS POTENTIAL CARBONIC ANHYDRASES (CAI-CAII) INHIBITORS. J. Fac. Pharm. Ankara. 2025;49:773–784.
MLA	Kedik, Cheeghdam et al. “SYNTHESIS AND CHARACTERIZATION OF NOVEL 5-FLOUROINDOLYLMETHYLEN HYDRAZON DERIVATIVES AS SCHIFF BASE COMPONDS: IN VITRO AND IN SILICO EVALUATION AS POTENTIAL CARBONIC ANHYDRASES (CAI-CAII) INHIBITORS”. Journal of Faculty of Pharmacy of Ankara University, vol. 49, no. 3, 2025, pp. 773-84, doi:10.33483/jfpau.1648214.
Vancouver	Kedik C, Faydalı N, Dilek E, Şirinzade H. SYNTHESIS AND CHARACTERIZATION OF NOVEL 5-FLOUROINDOLYLMETHYLEN HYDRAZON DERIVATIVES AS SCHIFF BASE COMPONDS: IN VITRO AND IN SILICO EVALUATION AS POTENTIAL CARBONIC ANHYDRASES (CAI-CAII) INHIBITORS. J. Fac. Pharm. Ankara. 2025;49(3):773-84.

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The Journal of Faculty of Pharmacy of Ankara University is an international medium, an open access, peer-reviewed journal for the publication of original research reports, reviews and short communications in English or Turkish on relevant developments in pharmaceutical sciences., Proceeding of scientific meetings may be published as special issues of supplements to the journal. Additionally, it contains previous and forthcoming national and international scientific meetings with social activities in pharmaceutical areas.