Evaluation of Newly Synthesized Compounds Targeting Carbonic Anhydrase Enzyme for Antineoplastic Activity in Solid Tumors


  • Esraa M. Naji Pharmaceutical chemistry department, Faculty of Pharmacy, Kufa University, Najaf, Iraq.
  • Sahar A. Hussein Pharmaceutical chemistry department, Faculty of pharmacy, Kufa University, Najaf, Iraq.
  • Noor H. Naser Pharmaceutical chemistry department, College of Pharmacy, Al-Zahraa University for women, Karbala, Iraq.




Sulfonamide, Thiazole ring, Docking study


Objective: This study was conducted with the aim of assessing the antineoplastic potential of recently developed compounds, namely F3, F4, and F5. These compounds were designed to target the carbonic anhydrase enzyme in solid tumors.

Methods: The synthesis of these compounds involved the utilization of sulfanilamide, chloroacetylchloride, thiourea, benzyl chloride derivatives, and silver nitrate. Docking studies were carried out using the MOE software program version 2015.10, and the cytotoxic activity was predicted through the implementation of the MTT assay.

Results: The compounds that were synthesized displayed noteworthy antineoplastic activity, as evidenced by both in silico simulations and cell line investigations. Notably, Compound F5 exhibited an IC50 value of 9.02 μg/ml for MCF7 cells, signifying a substantial difference when compared to the IC50 value of cisplatin. Moreover, Compounds F3 and F4 exhibited higher S scores in the docking study compared to acetazolamide, implying a more robust binding affinity to the catalytic site of the receptor. The inclusion of a substituted thiazole ring contributed to increased flexibility and enhanced receptor interaction.

Conclusion: The synthetic compounds put forth in this study demonstrated notable antineoplastic properties. Furthermore, the complexation process notably augmented the inhibition of cancer cell growth, underscoring their potential as promising agents for combating cancer.


Bukowski, K., M. Kciuk, and R. Kontek, Mechanisms of multidrug resistance in cancer chemotherapy. International journal of molecular sciences, 2020. 21(9): p. 3233.

Sunjuk, M., et al., Transition Metal Complexes of Schiff Base Ligands Prepared from Reaction of Aminobenzothiazole with Benzaldehydes. Inorganics, 2022. 10(4): p. 43.

Mansoori, B., et al., The different mechanisms of cancer drug resistance: a brief review. Advanced pharmaceutical bulletin, 2017. 7(3): p. 339.

Dallavalle, S., et al., Improvement of conventional anti-cancer drugs as new tools against multidrug resistant tumors. Drug Resistance Updates, 2020. 50: p. 100682.

Butturini, E., et al., Tumor dormancy and interplay with hypoxic tumor microenvironment. International journal of molecular sciences, 2019. 20(17): p. 4305.

Mussi, S., et al., Antiproliferative effects of sulphonamide carbonic anhydrase inhibitors C18, SLC-0111 and acetazolamide on bladder, glioblastoma and pancreatic cancer cell lines. Journal of Enzyme Inhibition and Medicinal Chemistry, 2022. 37(1): p. 280-286.

Supuran, C.T., Structure and function of carbonic anhydrases. Biochemical Journal, 2016. 473(14): p. 2023-2032.

Angeli, A., et al., Pyrazolo [4, 3-c] pyridine Sulfonamides as Carbonic Anhydrase Inhibitors: Synthesis, Biological and In Silico Studies. Pharmaceuticals, 2022. 15(3): p. 316.

Khushal, A., et al., Synthesis, carbonic anhydrase II/IX/XII inhibition, DFT, and molecular docking studies of hydrazide-sulfonamide hybrids of 4-methylsalicyl-and acyl-substituted hydrazide. BioMed Research International, 2022. 2022.

Supuran, C.T., et al., Carbonic anhydrase inhibitors: sulfonamides as antitumor agents? Bioorganic & medicinal chemistry, 2001. 9(3): p. 703-714.

Supuran, C.T., Experimental carbonic anhydrase inhibitors for the treatment of hypoxic tumors. Journal of Experimental Pharmacology, 2020: p. 603-617.

Angeli, A., et al., Carbonic anhydrase inhibitors targeting metabolism and tumor microenvironment. Metabolites, 2020. 10(10): p. 412.

Said, M.A., et al., Sulfonamide-based ring-fused analogues for CAN508 as novel carbonic anhydrase inhibitors endowed with antitumor activity: Design, synthesis, and in vitro biological evaluation. European Journal of Medicinal Chemistry, 2020. 189: p. 112019.

Borcea, A.-M., et al., An overview of the synthesis and antimicrobial, antiprotozoal, and antitumor activity of thiazole and bisthiazole derivatives. Molecules, 2021. 26(3): p. 624.

Sharma, P.C., et al., Thiazole-containing compounds as therapeutic targets for cancer therapy. European journal of medicinal chemistry, 2020. 188: p. 112016.

Ramos-Inza, S., et al., Thiazole moiety: An interesting scaffold for developing new antitumoral compounds, in Heterocycles-synthesis and biological activities. 2019, IntechOpen.

Arshad, M.F., et al., Thiazole: A versatile standalone moiety contributing to the development of various drugs and biologically active agents. Molecules, 2022. 27(13): p. 3994.

Supuran, C.T., A. Scozzafava, and A. Casini, Carbonic anhydrase inhibitors. Medicinal research reviews, 2003. 23(2): p. 146-189.

Billah, M.M., et al., Determination of the presence and pharmacokinetic profile of ciprofloxacin by TLC and HPLC method respectively in broiler chicken after single oral administration. The Journal of Antibiotics, 2014. 67(11): p. 745-748.

Saeedi, M., et al., Synthesis and biological investigation of some novel sulfonamide and amide derivatives containing coumarin moieties. Iranian Journal of Pharmaceutical Research: IJPR, 2014. 13(3): p. 881.

Jawad, H.A., et al., Design, Synthesis, In Silico Study And Preliminary Pharmacological Assessment Of New Ciprofloxacin Analogues Having Thiazole Nucleus. Journal of Pharmaceutical Negative Results, 2023: p. 91-104.

Park, H.-S., et al., Synthesis and characterization of novel hydantoins as potential COX-2 inhibitors: 1, 5-Diarylhydantoins. Bulletin of the Korean Chemical Society, 2007. 28(5): p. 751-757.



How to Cite

Naji, E. M. ., Hussein, S. A. ., & Naser, N. H. . (2023). Evaluation of Newly Synthesized Compounds Targeting Carbonic Anhydrase Enzyme for Antineoplastic Activity in Solid Tumors. Journal of Contemporary Medical Sciences, 9(4). https://doi.org/10.22317/jcms.v9i4.1394