Design and Synthesis of Some New Benzoylthioureido Phenyl Derivatives Targeting Carbonic Anhydrase Enzymes

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2022 Sep 28

PMID 36168122

Authors

Mazin A A Najm

Walaa R Mahmoud

Azza T Taher

Safinaz E-S Abbas

Fadi M Awadallah

Heba Abdelrasheed Allam

Daniela Vullo

Claudiu T Supuran

Affiliations

Soon will be listed here.

Abstract

The present study aimed to develop potent carbonic anhydrase inhibitors (CAIs). The design of the target compounds was based on modifying the structure of the ureido-based carbonic anhydrase inhibitor SLC-0111. Six series of a substituted benzoylthioureido core were prepared featuring different zinc-binding groups; the conventional sulphamoyl group and , its bioisosteric carboxylic acid group and or the ethyl carboxylate group and as potential prodrugs. All compounds were assessed for their carbonic anhydrase (CA) inhibitory activity against a panel of four physiologically relevant human CA isoforms hCA I and hCA II, and hCA IX, and hCA XII. Compounds , , , , and revealed significant inhibitory activity against hCA I that would highlight these compounds as promising drug candidates for the treatment of glaucoma.

Citing Articles

Sulphonyl thiourea compounds containing pyrimidine as dual inhibitors of I, II, IX, and XII carbonic anhydrases and cancer cell lines: synthesis, characterization and studies.

Thanh N, Toan V, Trang V RSC Med Chem. 2025; .

PMID: 39823041 PMC: 11734695. DOI: 10.1039/d4md00816b.

Carbonic anhydrase inhibitory activity of phthalimide-capped benzene sulphonamide derivatives.

Shilkar D, Siddique M, Bua S, Yasmin S, Patil M, Timiri A J Enzyme Inhib Med Chem. 2023; 38(1):2235089.

PMID: 37439360 PMC: 10348020. DOI: 10.1080/14756366.2023.2235089.

Identification of specific carbonic anhydrase inhibitors click chemistry, phage-display and synthetic peptide libraries: comparison of the methods and structural study.

Kugler M, Hadzima M, Dzijak R, Rampmaier R, Srb P, Vrzal L RSC Med Chem. 2023; 14(1):144-153.

PMID: 36760748 PMC: 9890587. DOI: 10.1039/d2md00330a.

Investigation of novel alkyl/benzyl (4-sulphamoylphenyl)carbamimidothioates as carbonic anhydrase inhibitors.

Abdoli M, Bonardi A, Supuran C, Zalubovskis R J Enzyme Inhib Med Chem. 2023; 38(1):2152811.

PMID: 36629134 PMC: 9848269. DOI: 10.1080/14756366.2022.2152811.

References

Elbadawi M, Eldehna W, Nocentini A, Abo-Ashour M, Elkaeed E, Abdelgawad M . Identification of N-phenyl-2-(phenylsulfonyl)acetamides/propanamides as new SLC-0111 analogues: Synthesis and evaluation of the carbonic anhydrase inhibitory activities. Eur J Med Chem. 2021; 218:113360. DOI: 10.1016/j.ejmech.2021.113360. View

Angeli A, Carta F, Nocentini A, Winum J, Zalubovskis R, Akdemir A . Carbonic Anhydrase Inhibitors Targeting Metabolism and Tumor Microenvironment. Metabolites. 2020; 10(10). PMC: 7602163. DOI: 10.3390/metabo10100412. View

Pacchiano F, Carta F, McDonald P, Lou Y, Vullo D, Scozzafava A . Ureido-substituted benzenesulfonamides potently inhibit carbonic anhydrase IX and show antimetastatic activity in a model of breast cancer metastasis. J Med Chem. 2011; 54(6):1896-902. DOI: 10.1021/jm101541x. View

Ghorai S, Pulya S, Ghosh K, Panda P, Ghosh B, Gayen S . Structure-activity relationship of human carbonic anhydrase-II inhibitors: Detailed insight for future development as anti-glaucoma agents. Bioorg Chem. 2020; 95:103557. DOI: 10.1016/j.bioorg.2019.103557. View

Mahdavi M, Shahzad Shirazi M, Taherkhani R, Saeedi M, Alipour E, Moghadam F . Synthesis, biological evaluation and docking study of 3-aroyl-1-(4-sulfamoylphenyl)thiourea derivatives as 15-lipoxygenase inhibitors. Eur J Med Chem. 2014; 82:308-13. DOI: 10.1016/j.ejmech.2014.05.054. View

Zhang Z, Lau J, Zhang C, Colpo N, Nocentini A, Supuran C . Design, synthesis and evaluation of F-labeled cationic carbonic anhydrase IX inhibitors for PET imaging. J Enzyme Inhib Med Chem. 2017; 32(1):722-730. PMC: 6445240. DOI: 10.1080/14756366.2017.1308928. View

Chiche J, Ilc K, Laferriere J, Trottier E, Dayan F, Mazure N . Hypoxia-inducible carbonic anhydrase IX and XII promote tumor cell growth by counteracting acidosis through the regulation of the intracellular pH. Cancer Res. 2009; 69(1):358-68. DOI: 10.1158/0008-5472.CAN-08-2470. View

Saeed S, Bhatti M, Yunus U, Jones P . Ethyl 4-(3-benzoyl-thio-ureido)benzoate. Acta Crystallogr Sect E Struct Rep Online. 2011; 64(Pt 8):o1485. PMC: 2962115. DOI: 10.1107/S1600536808017856. View

Neri D, Supuran C . Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discov. 2011; 10(10):767-77. DOI: 10.1038/nrd3554. View

10.

Darin D, Kantin G, Kalinin S, Sharonova T, Bunev A, Ostapenko G . Investigation of 3-sulfamoyl coumarins against cancer-related IX and XII isoforms of human carbonic anhydrase as well as cancer cells leads to the discovery of 2-oxo-2H-benzo[h]chromene-3-sulfonamide - A new caspase-activating proapoptotic agent. Eur J Med Chem. 2021; 222:113589. DOI: 10.1016/j.ejmech.2021.113589. View

11.

Nocentini A, Vullo D, Del Prete S, Osman S, Alasmary F, Alothman Z . Inhibition of the β-carbonic anhydrase from the dandruff-producing fungus Malassezia globosa with monothiocarbamates. J Enzyme Inhib Med Chem. 2017; 32(1):1064-1070. PMC: 6010091. DOI: 10.1080/14756366.2017.1355307. View

12.

Elimam D, Elgazar A, Bonardi A, Abdelfadil M, Nocentini A, El-Domany R . Natural inspired piperine-based sulfonamides and carboxylic acids as carbonic anhydrase inhibitors: Design, synthesis and biological evaluation. Eur J Med Chem. 2021; 225:113800. DOI: 10.1016/j.ejmech.2021.113800. View

13.

Gieling R, Williams K . Carbonic anhydrase IX as a target for metastatic disease. Bioorg Med Chem. 2012; 21(6):1470-6. DOI: 10.1016/j.bmc.2012.09.062. View

14.

Heravi Y, Bua S, Nocentini A, Del Prete S, Saboury A, Sereshti H . Inhibition of Malassezia globosa carbonic anhydrase with phenols. Bioorg Med Chem. 2017; 25(9):2577-2582. DOI: 10.1016/j.bmc.2017.03.026. View

15.

Vullo D, Lehneck R, Donald W, Poggeler S, Supuran C . Sulfonamide Inhibition Studies of the β-Class Carbonic Anhydrase CAS3 from the Filamentous Ascomycete . Molecules. 2020; 25(5). PMC: 7179226. DOI: 10.3390/molecules25051036. View

16.

Pacchiano F, Aggarwal M, Avvaru B, Robbins A, Scozzafava A, McKenna R . Selective hydrophobic pocket binding observed within the carbonic anhydrase II active site accommodate different 4-substituted-ureido-benzenesulfonamides and correlate to inhibitor potency. Chem Commun (Camb). 2010; 46(44):8371-3. DOI: 10.1039/c0cc02707c. View

17.

Nitulescu G, Draghici C, Olaru O . New potential antitumor pyrazole derivatives: synthesis and cytotoxic evaluation. Int J Mol Sci. 2013; 14(11):21805-18. PMC: 3856036. DOI: 10.3390/ijms141121805. View

18.

Abo-Ashour M, Eldehna W, Nocentini A, Ibrahim H, Bua S, Abdel-Aziz H . Novel synthesized SLC-0111 thiazole and thiadiazole analogues: Determination of their carbonic anhydrase inhibitory activity and molecular modeling studies. Bioorg Chem. 2019; 87:794-802. DOI: 10.1016/j.bioorg.2019.04.002. View

19.

El-Sayed N, El-Bendary E, El-Ashry S, El-Kerdawy M . Synthesis and antitumor activity of new sulfonamide derivatives of thiadiazolo[3,2-a]pyrimidines. Eur J Med Chem. 2011; 46(9):3714-20. DOI: 10.1016/j.ejmech.2011.05.037. View

20.

Nocentini A, Bua S, Lomelino C, McKenna R, Menicatti M, Bartolucci G . Discovery of New Sulfonamide Carbonic Anhydrase IX Inhibitors Incorporating Nitrogenous Bases. ACS Med Chem Lett. 2017; 8(12):1314-1319. PMC: 5733260. DOI: 10.1021/acsmedchemlett.7b00399. View