ABSTRACT:

Aim: Design, molecular docking, synthesis, and evaluation of cytotoxic activity of new compounds I, II, III, and IV that have isatin-sulfonamide derivatives.
Materials and Methods: for chemical synthesis, chemical compounds such as sulfonamide, 4-amino ethyl benzoate, isatin, and its derivatives were used. For the docking study (MOE), software program version 2015.10 was used. The MTT assay was utilized to predict the cytotoxic activity.
Results: The synthesized compounds demonstrated significant inhibition of carbonic anhydrase XII activity through molecular docking, as well as significant inhibition of cancer cell viability. Compounds II and IV show higher S-scores than acetazolamide. Also, the MTT assay shows that compounds II and IV have IC50 values of 0.06 µM and 0.105 µM against MCF-7 cells, respectively, while acetazolamide has an IC50 value of 0.394 µM. While acetazolamide had an IC50 of 0.901 µM, compounds II and IV had IC50s of 0.063 µM and 0.114 µM against Hct116 cells, respectively. The MTT assay explains compounds II and IV have better cytotoxic activity compared with acetazolamide.
Conclusion: New compounds that were produced showed signs of cytotoxicity and carbonic anhydrase inhibitory qualities.

KEYWORDS:

carbonic anhydrase, sulfonamide, docking study

REFERENCES :

1) Siegel, R. L., Miller, K. D., & Jemal, A. (2019). Cancer statistics, 2019. CA: a cancer journal for clinicians, 69(1), 7-34.‏) (Zaorsky, N. G., Churilla, T. M., Egleston, B. L., Fisher, S. G., Ridge, J. A., Horwitz, E. M., & Meyer, J. E. (2017). Causes of death among cancer patients. Annals of oncology, 28(2), 400-407. ‏
2) Alibeg, A. A. A., Abdulsada, A. H., Nasser, N. H., & Ali Beg, K. A. A. (2020). Design and synthesis of possible mutual prodrugs of (nsaid) etodolac and tolmetin with (cytotoxic) gemcitabine. Syst. Rev. Pharm, 11(11), 315-318.‏
3) Dorak, M. T., & Karpuzoglu, E. (2012). Gender differences in cancer susceptibility: an inadequately addressed issue. Frontiers in genetics, 3, 268.‏
4) (Edgren, G., Liang, L., Adami, H. O., & Chang, E. T. (2012). Enigmatic sex disparities in cancer incidence. European journal of epidemiology, 27, 187-196.‏
5) Machlowska, J., Baj, J., Sitarz, M., Maciejewski, R., & Sitarz, R. (2020). Gastric cancer: epidemiology, risk factors, classification, genomic characteristics and treatment strategies. International journal of molecular sciences, 21(11), 4012.‏
6) Shaldam, M. A., Almahli, H., Angeli, A., Badi, R. M., Khaleel, E. F., Zain-Alabdeen, A. I., … & Tawfik, H. O. (2023). Discovery of sulfonamide-tethered isatin derivatives as novel anticancer agents and VEGFR-2 inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, 38(1), 2203389.‏
7) Naji, E. M., Naser, N. H., & Hussein, S. A. (2023). In silico study, synthesis, and antineoplastic evaluation of thiazole-based sulfonamide derivatives and their silver complexes with expected carbonic anhydrase inhibitory activity. Journal of Medicine and Life, 16(12), 1857.‏
8) Noor, H., β-Carbonic Anhydrase as a Target for Eradication of Mycobacterium tuberculosis
9) Aljubouri, R. S., & Naser, N. H. (2023). In Silico Study of New Carbonic Anhydrase Inhibitor Derivatives Bearing 1, 3, 4-Oxadiazole Moiety with Promising Anti-Cancer Activity. Journal of Contemporary Medical Sciences, 9(5).‏
10) Aggarwal, M. (2013). Insights into human carbonic anhydrase inhibitor design (Doctoral dissertation, University of Florida).‏
11) Sağlık, B. N., Cevik, U. A., Osmaniye, D., Levent, S., Çavuşoğlu, B. K., Demir, Y., … & Kaplancıklı, Z. A. (2019). Synthesis, molecular docking analysis and carbonic anhydrase I-II inhibitory evaluation of new sulfonamide derivatives. Bioorganic chemistry, 91, 103153.
12) Tafreshi, N. K., Lloyd, M. C., Bui, M. M., Gillies, R. J., & Morse, D. L. (2014). Carbonic anhydrase IX as an imaging and therapeutic target for tumors and metastases. Carbonic anhydrase: Mechanism, regulation, links to disease, and industrial applications, 221-254.‏)
13) Salerno, S., Amendola, G., Angeli, A., Baglini, E., Barresi, E., Marini, A. M., … & Taliani, S. (2021). Inhibition studies on carbonic anhydrase isoforms I, II, IV and IX with N-arylsubstituted secondary sulfonamides featuring a bicyclic tetrahydroindazole scaffold. European Journal of Medicinal Chemistry, 220, 113490.‏
14) Abbas, Z. K., Naser, N. H., & Atiya, R. N. (2023). Targeting the Carbonic Anhydrase Enzyme with Synthesized Benzenesulfonamide Derivatives: Inhibiting Tumor Growth. Journal of Contemporary Medical Sciences, 9(4).‏ Al-Khuzaie, M. G., Fahad, M. M., & Al-Safi, A. J. (2022). Synthesis, reaction and biological importance of isatin derivatives. Biomedicine and Chemical Sciences, 1(3), 193-206.‏
15) Al-Khuzaie, M. G., Fahad, M. M., & Al-Safi, A. J. (2022). Synthesis, reaction and biological importance of isatin derivatives. Biomedicine and Chemical Sciences, 1(3), 193-206.‏
16) Alibeg AAA, Mohammed MH. Design, synthesis, insilco study and biological evaluation of new isatin-sulfonamide derivatives by using mono amide linker as possible as histone deacetylase inhibitors. Pol Merkur Lekarski. 2024;52(2):178-188. doi: 10.36740/Merkur 202402106. PMID: 38642353.
17) Altalhi, A. A. (2024). Novel N-heterocyclic Schiff base based on Isatin derivative as a sustainable, eco-friendly, and highly efficiency corrosion inhibitor for carbon steel in sulfuric acid medium: Electrochemical and Computational investigation. International Journal of Electrochemical Science, 19(1), 100449.‏
18) Alibeg AAA, Mohammed MH. Molecular docking, synthesis, characteristics and preliminary cytotoxic study of new coumarin-sulfonamide derivatives as histone deacetylase inhibitors. Wiad Lek. 2024;77(3):514-525. doi: 10.36740/WLek202403118. PMID: 38691794.
19) Patil, J. V., Umar, S., Soni, R., Soman, S. S., & Balakrishnan, S. (2023). Design, synthesis and anticancer activity of amide derivatives of substituted 3-methyl-benzofuran-2-carboxylic acid. Synthetic Communications, 53(3), 217-233.‏
20) Pavia, D.L., et al., Introduction to spectroscopy. 2014: Cengage learning.
21) Tuğrak, M., Gül, H. İ., Sakagami, H., Kaya, R., & Gülçin, İ. (2021). Synthesis and biological evaluation of new pyrazolebenzene-sulphonamides as potentialanticancer agents and hCA I and II inhibitors. Turkish Journal of Chemistry, 45(3), 528-539.‏