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Research Article

Design, synthesis, and biological investigation of selective human carbonic anhydrase II, IX, and XII inhibitors using 7-aryl/heteroaryl triazolopyrimidines bearing a sulfanilamide scaffold

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Article: 2270180 | Received 17 Jul 2023, Accepted 07 Oct 2023, Published online: 18 Oct 2023

References

  • Supuran CT. Structure and function of carbonic anhydrases. Biochem J. 2016;473(14):2023–2032.
  • Krishnamurthy VM, Kaufman GK, Urbach AR, Gitlin I, Gudiksen KL, Weibel DB, Whitesides GM. Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein–ligand binding. Chem Rev. 2008;108(3):946–1051.
  • Jensen EL, Clement R, Kosta A, Maberly SC, Gontero B. A new widespread subclass of carbonic anhydrase in marine phytoplankton. ISME J. 2019;13(8):2094–2106.
  • Aspatwar A, Haapanen S, Parkkila S. An update on the metabolic roles of carbonic anhydrases in the model alga Chlamydomonas reinhardtii. Metabolites. 2018;8(1):22.
  • Kupriyanova E, Pronina N, Los D. Carbonic anhydrase—a universal enzyme of the carbon-based life. Photosynthetica. 2017;55(1):3–19.
  • Supuran CT, De Simone G. Carbonic anhydrases: an overview. In: Supuran CT, De Simone G, editors. Carbonic anhydrases as biocatalysts. From theory to medical and industrial applications. Amsterdam: Elsevier; 2015.
  • Henry RP. Multiple roles of carbonic anhydrase in cellular transport and metabolism. Annu Rev Physiol. 1996;58(1):523–538.
  • Geers C, Gros G. Carbon dioxide transport and carbonic anhydrase in blood and muscle. Physiol Rev. 2000;80(2):681–715.
  • Alterio V, Di Fiore A, D'Ambrosio K, Supuran CT, De Simone G. Multiple binding modes of inhibitors to carbonic anhydrases: how to design specific drugs targeting 15 different isoforms? Chem Rev. 2012;112(8):4421–4468.
  • Supuran CT, Capasso C. Chapter 13 – a catalytic carbonic anhydrases (CAs VIII, X, XI). In: Supuran CT, De Simone G, editors. Carbonic anhydrases as biocatalysts. Amsterdam: Elsevier; 2015. p. 239–245.
  • D’Ambrosio K, De Simone G, Supuran CT. Chapter 2 - Human carbonic anhydrases: catalytic properties, structural features, and tissue distribution. In: Supuran CT, De Simone G, editors. Carbonic anhydrases as biocatalysts. Amsterdam: Elsevier; 2015. p. 17–30.
  • Supuran CT. How many carbonic anhydrase inhibition mechanisms exist? J Enzyme Inhib Med Chem. 2016;31(3):345–360.
  • Nocentini A, Supuran CT. Advances in the structural annotation of human carbonic anhydrases and impact on future drug discovery. Expert Opin Drug Discov. 2019;14(11):1175–1197.
  • Supuran CT. Emerging role of carbonic anhydrase inhibitors. Clin Sci. 2021;135(10):1233–1249.
  • Supuran CT. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat Rev Drug Discov. 2008;7(2):168–181.
  • Aspatwar A, Tolvanen MEE, Barker H, Syrjänen L, Valanne S, Purmonen S, Waheed A, Sly WS, Parkkila S. Carbonic anhydrases in metazoan model organisms: molecules, mechanisms, and physiology. Physiol Rev. 2022;102(3):1327–1383.
  • Supuran CT. Structure-based drug discovery of carbonic anhydrase inhibitors. J Enzyme Inhib Med Chem. 2012;27(6):759–772.
  • Nocentini A, Supuran CT, Capasso C. An overview on the recently discovered iota-carbonic anhydrases. J Enzyme Inhib Med Chem. 2021;36(1):1988–1995.
  • Buabeng ER, Henary M. Developments of small molecules as inhibitors for carbonic anhydrase isoforms. Bioorg Med Chem. 2021;39:116140.
  • Supuran CT. Novel carbonic anhydrase inhibitors. Future Med Chem. 2021;13:1935–1937.
  • Eldehna WM, Fares M, Ceruso M, Ghabbour HA, Abou-Seri SM, Abdel-Aziz HA, Abou El Ella DA, Supuran CT. Amido/ureidosubstituted benzenesulfonamides-isatin conjugates as low nanomolar/subnanomolar inhibitors of the tumor-associated carbonic anhydrase isoform XII. Eur J Med Chem. 2016;110:259–266.
  • Thiry A, Dogné J-M, Supuran CT, Masereel B. Carbonic anhydrase inhibitors as anticonvulsant agents. Curr Top Med Chem. 2007;7(9):855–864.
  • Mishra CB, Tiwari M, Supuran CT. Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: where are we today? Med Res Rev. 2020;40(6):2485–2565.
  • Supuran CT. Advances in structure-based drug discovery of carbonic anhydrase inhibitors. Expert Opin Drug Discov. 2017;12(1):61–88.
  • Supuran CT. Carbonic anhydrase inhibitors: an update on experimental agents for the treatment and imaging of hypoxic tumors. Expert Opin Investig Drugs. 2021;30(12):1197–1208.
  • McDonald PC, Chafe SC, Supuran CT, Dedhar S. Cancer therapeutic targeting of hypoxia induced carbonic anhydrase IX: from bench to bedside. Cancers. 2022;14(14):3297.
  • Supuran CT. Experimental carbonic anhydrase inhibitors for the treatment of hypoxic tumors. J Exp Pharmacol. 2020;12:603–617.
  • Potter C, Harris AL. Hypoxia inducible carbonic anhydrase IX, marker of tumour hypoxia, survival pathway and therapy target. Cell Cycle. 2004;3(2):159–162.
  • Pastorekova S, Zatovicova M, Pastorek J. Cancer-associated carbonic anhydrases and their inhibition. Curr Pharm Des. 2008;14(7):685–698.
  • Lee SH, McIntyre D, Honess D, Hulikova A, Pacheco-Torres J, Cerdan S, Swietach P, Harris AL, Griffiths JR. Carbonic anhydrase IX is a pH-stat that sets an acidic tumour extracellular pH in vivo. Br J Cancer. 2018;119(5):622–630.
  • Chiche J, Ilc K, Laferrière J, Trottier E, Dayan F, Mazure NM, Brahimi-Horn MC, Pouysségur J. 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):358–368.
  • De Simone G, Supuran CT. Carbonic anhydrase IX: biochemical and crystallographic characterization of a novel antitumor target. Biochim Biophys Acta. 2010;1804(2):404–409.
  • Neri D, Supuran CT. Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discov. 2011;10(10):767–777.
  • Pastorek J, Pastorekova S. Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: from biology to clinical use. Semin Cancer Biol. 2015;31:52–64.
  • Kopecka J, Campia I, Jacobs A, Frei AP, Ghigo D, Wollscheid B, Riganti C. Carbonic anhydrase XII is a new therapeutic target to overcome chemoresistance in cancer cells. Oncotarget. 2015;6(9):6776–6793.
  • Ulmasov B, Waheed A, Shah GN, Grubb JH, Sly WS, Tu C, Silverman DN. Purification and kinetic analysis of recombinant CA XII, a membrane carbonic anhydrase overexpressed in certain cancers. Proc Natl Acad Sci U S A. 2000;97(26):14212–14217.
  • Wichert M, Krall N. Targeting carbonic anhydrase IX with small organic ligands. Curr Opin Chem Biol. 2015;26:48–54.
  • Supuran CT, Alterio V, Di Fiore A, D' Ambrosio K, Carta F, Monti SM, De Simone G. Inhibition of carbonic anhydrase IX targets primary tumors, metastases, and cancer stem cells: three for the price of one. Med Res Rev. 2018;38(6):1799–1836.
  • Pacchiano F, Carta F, McDonald PC, Lou Y, Vullo D, Scozzafava A, Dedhar S, Supuran CT. 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):1896–1902.
  • Dar’in D, Kantin G, Kalinin S, Sharonova T, Bunev A, Ostapenko GI, Nocentini A, Sharoyko V, Supuran CT, Krasavin M. 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.
  • McDonald PC, Winum JY, Supuran CT, Dedhar S. Recent developments in targeting carbonic anhydrase IX for cancer therapeutics. Oncotarget. 2012;3(1):84–97.
  • Noor SI, Jamali S, Ames S, Langer S, Deitmer JW, Becker HM. A surface proton antenna in carbonic anhydrase II supports lactate transport in cancer cells. eLife. 2018;7:e35176.
  • Leppilampi M, Koistinen P, Savolainen ER, Hannuksela J, Parkkila AK, Niemela O, Pastorekova S, Pastorek J, Waheed A, Sly WS, et al. The expression of carbonic anhydrase II in hematological malignancies. Clin Cancer Res. 2002;8:2240–2245.
  • Zhou R, Huang W, Yao Y, Wang Y, Li Z, Shao B, Zhong J, Tang M, Liang S, Zhao X, et al. CA II, a potential biomarker by proteomic analysis, exerts significant inhibitory effect on the growth of colorectal cancer cells. Int J Oncol. 2013;43(2):611–621.
  • Parkkila S, Lasota J, Fletcher JA, Ou WB, Kivela AJ, Nuorva K, Parkkila AK, Ollikainen J, Sly WS, Waheed A, et al. Carbonic anhydrase II. A novel biomarker for gastrointestinal stromal tumors. Mod Pathol. 2010;23(5):743–750.
  • Haapasalo J, Nordfors K, Haapasalo H, Parkkila S. The expression of carbonic anhydrases II, IX and XII in brain tumors. Cancers. 2020;12(7):1723.
  • Zhang H, Zhuo C, Zhou D, Zhang F, Chen M, Xu S, Chen Z. Association between the expression of carbonic anhydrase II and clinicopathological features of hepatocellular carcinoma. Oncol Lett. 2019;17(6):5721–5728.
  • Abdelrahman MA, Ibrahim HS, Nocentini A, Eldehna WM, Bonardi A, Abdel-Aziz HA, Gratteri P, Abou-Seri SM, Supuran CT. Novel 3-substituted coumarins as selective human carbonic anhydrase IX and XII inhibitors: synthesis, biological and molecular dynamics analysis. Eur J Med Chem. 2021;209:112897.
  • Mboge MY, McKenna R, Frost SC. Advances in anti-cancer drug development targeting carbonic anhydrase IX and XII. Top Anticancer Res. 2015;5:3–42.
  • Swenson ER. Safety of carbonic anhydrase inhibitors. Expert Opin Drug Saf. 2014;13:459–472.
  • Akocak S, Ilies MA. Next-generation primary sulfonamide carbonic anhydrase inhibitors. In: Supuran CT, Cappasso C, editors. Targeting carbonic anhydrases. London: Future Science; 2014. p. 35–51.
  • Vats L, Kumar R, Bua S, Nocentini A, Gratteri P, Supuran CT, Sharma PK. Continued exploration and tail approach synthesis of benzenesulfonamides containing triazole and dual triazole moieties as carbonic anhydrase I, II, IV and IX inhibitors. Eur J Med Chem. 2019;183:111698.
  • Carta F, Supuran CT, Scozzafava A. Sulfonamides and their isosters as carbonic anhydrase inhibitors. Future Med Chem. 2014;6(10):1149–1165.
  • Kumar A, Siwach K, Supuran CT, Sharma PK. A decade of tail-approach based design of selective as well as potent tumor associated carbonic anhydrase inhibitors. Bioorg Chem. 2022;126:105920.
  • Bozdag M, Ferraroni M, Nuti E, Vullo D, Rossello A, Carta F, Scozzafava A, Supuran CT. Combining the tail and the ring approaches for obtaining potent and isoform-selective carbonic anhydrase inhibitors: solution and X-ray crystallographic studies. Bioorg Med Chem. 2014;22(1):334–340.
  • Liguori F, Carradori S, Ronca R, Rezzola S, Filiberti S, Carta F, Turati M, Supuran CT. Benzenesulfonamides with different rigidity-conferring linkers as carbonic anhydrase inhibitors: an insight into the antiproliferative effect on glioblastoma, pancreatic, and breast cancer cells. J Enzyme Inhib Med Chem. 2022;37(1):1857–1869.
  • Wilkinson BL, Bornaghi LF, Houston TA, Innocenti A, Supuran CT, Poulsen SA. A novel class of carbonic anhydrase inhibitors: glycoconjugate benzene sulfonamides prepared by "click-tailing". J Med Chem. 2006;49(22):6539–6548.
  • Fares M, Eldehna WM, Bua S, Lanzi C, Lucarini L, Masini E, Peat TS, Abdel-Aziz HA, Nocentini A, Keller PA, et al. Discovery of potent dual-tailed benzenesulfonamide inhibitors of human carbonic anhydrases implicated in glaucoma and in vivo profiling of their intraocular pressure-lowering action. J Med Chem. 2020;63(6):3317–3326.
  • Allam HA, Fahim SH, Abo-Ashour MF, Nocentini A, Elbakry ME, Abdelrahman MA, Eldehna WM, Ibrahim HS, Supuran CT. Application of hydrazino and hydrazido linkers to connect benzenesulfonamides with hydrophilic/phobic tails for targeting the middle region of human carbonic anhydrases active site: selective inhibitors of hCA IX. Eur J Med Chem. 2019;179:547–556.
  • Ibrahim HS, Allam HA, Mahmoud WR, Bonardi A, Nocentini A, Gratteri P, Ibrahim ES, Abdel-Aziz HA, Supuran CT. Dual-tail arylsulfone-based benzenesulfonamides differently match the hydrophobic and hydrophilic halves of human carbonic anhydrases active sites: selective inhibitors for the tumor-associated hCA IX isoform. Eur J Med Chem. 2018;152:1–9.
  • Tanpure RP, Ren B, Peat TS, Bornaghi LF, Vullo D, Supuran CT, Poulsen SA. Carbonic anhydrase inhibitors with dual-tail moieties to match the hydrophobic and hydrophilic halves of the carbonic anhydrase active site. J Med Chem. 2015;58(3):1494–1501.
  • Stams T, Christianson DW. X-ray crystallographic studies of mammalian carbonic anhydrase isozymes. In: Chegwidden WR, Carter ND, Edwards YH, editors. The carbonic anhydrases. EXS 90. Vol. 90. Basel: Birkhäuser; 2000. p. 159–174.
  • Carta F, Vullo D, Osman SM, Alothman ZA, Supuran CT. Synthesis and carbonic anhydrase inhibition of a series of SLC-0111 analogs. Bioorg Med Chem. 2017;25(9):2569–2576.
  • McDonald PC, Chia S, Bedard PL, Chu Q, Lyle M, Tang L, Singh M, Zhang Z, Supuran CT, Renouf DJ, et al. A phase 1 study of SLC-0111, a novel inhibitor of carbonic anhydrase IX, in patients with advanced solid tumors. Am J Clin Oncol. 2020;43(7):484–490.
  • Eldehna WM, Abo-Ashour MF, Berrino E, Vullo D, Ghabbour HA, Rashood ST, Hassan GS, Alkahtani HM, Almehizia AA, Alharbi A, Abdel-Aziz HA, et al. SLC-0111 enaminone analogues, 3/4-(3-aryl-3-oxopropenyl)aminobenzenesulfonamides, as novel selective subnanomolar inhibitors of the tumor-associated carbonic anhydrase isoform IX. Bioorg Chem. 2019;83:549–558.
  • Elbadawi MM, Eldehna WM, Nocentini A, Abo-Ashour MF, Elkaeed EB, Abdelgawad MA, Alharbi KS, Abdel-Aziz HA, Supuran CT, Gratteri P, et al. 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.
  • Eldehna WM, Abo-Ashour MF, Nocentini A, El-Haggar RS, Bua S, Bonardi A, Al-Rashood ST, Hassan GS, Gratteri P, Abdel-Aziz HA, et al. Enhancement of the tail hydrophobic interactions within the carbonic anhydrase IX active site via structural extension: design and synthesis of novel N-substituted isatins-SLC-0111 hybrids as carbonic anhydrase inhibitors and antitumor agents. Eur J Med Chem. 2019;162:147–160.
  • Dai X-J, Xue L-P, Ji S-K, Zhou Y, Gao Y, Zheng Y-C, Liu H-M, Liu H-M. Triazole-fused pyrimidines in target-based anticancer drug discovery. Eur J Med Chem. 2023;249:115101.
  • Mohamed HS, Amin NH, El-Saadi MT, Abdel-Rahman HM. Design, synthesis, biological assessment, and in-silico studies of 1,2,4-triazolo[1,5-a]pyrimidine derivatives as tubulin polymerization inhibitors. Bioorg Chem. 2022;121:105687.
  • Yang F, Yu LZ, Diao PC, Jian XE, Zhou MF, Jiang CS, You WW, Ma WF, Zhao PL. Novel [1,2,4]triazolo[1,5-a]pyrimidine derivatives as potent antitubulin agents: design, multicomponent synthesis and antiproliferative activities. Bioorg Chem. 2019;92:103260.
  • Huo XS, Jian XE, Ou-Yang J, Chen L, Yang F, Lv DX, You WW, Rao JJ, Zhao PL. Discovery of highly potent tubulin polymerization inhibitors: design, synthesis, and structure–activity relationships of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidines. Eur J Med Chem. 2021;220:113449.
  • Alle T, Varricchio C, Yao Y, Lucero B, Nzou G, Demuro S, Muench M, Vuong KD, Oukoloff K, Cornec A-S, et al. Microtubule-stabilizing 1,2,4-triazolo[1,5‑a]pyrimidines as candidate therapeutics for neurodegenerative disease: matched molecular pair analyses and computational studies reveal new structure–activity insights. J Med Chem. 2023;66(1):435–459.
  • Oliva P, Romagnoli R, Cacciari B, Manfredini S, Padroni C, Brancale A, Ferla S, Hamel E, Corallo D, Aveic S, et al. Synthesis and biological evaluation of highly active 7-anilino triazolopyrimidines as potent antimicrotubule agents. Pharmaceutics. 2022;14(6):1191.
  • Romagnoli R, Oliva P, Prencipe F, Manfredini S, Budassi F, Brancale A, Ferla S, Hamel E, Corallo D, Aveic S, et al. Design, synthesis and biological investigation of 2-anilino triazolopyrimidines as tubulin polymerization inhibitors with anticancer activities. Pharmaceuticals. 2022;15(8):1031.
  • Wang S, Shen DD, Zhao LJ, Yuan XH, Cheng JL, Yu B, Zheng YC, Liu HM. Discovery of [1,2,4]triazolo[1,5-a]pyrimidine derivatives as new bromodomain containing protein 4 (BRD4) inhibitors. Chin Chem Lett. 2020;31(2):418–422.
  • Wang S, Li ZR, Suo FZ, Yuan XH, Yu B, Liu HM. Synthesis, structure–activity relationship studies and biological characterization of new [1,2,4]triazolo[1,5-a]pyrimidine-based LSD1/KDM1A inhibitors. Eur J Med Chem. 2019;167:388–401.
  • Wang S, Zhao LJ, Zheng YC, Shen DD, Miao EF, Qiao XP, Zhao LJ, Liu Y, Huang R, Yu B, et al. Design, synthesis and biological evaluation of [1,2,4]triazolo[1,5-a]pyrimidines as potent lysine specific demethylase 1 (LSD1/KDM1A) inhibitors. Eur J Med Chem. 2017;125:940–951.
  • Wang S, Wang SQ, Teng QX, Yang L, Lei ZN, Yuan XH, Huo JF, Chen XB, Wang M, Yu B, et al. Structure-based design, synthesis, and biological evaluation of new triazolo[1,5-a]pyrimidine derivatives as highly potent and orally active ABCB1 modulators. J Med Chem. 2020;63(24):15979–15996.
  • Richardson CM, Williamson DS, Parratt MJ, Borgognoni J, Cansfield AD, Dokurno P, Francis GL, Howes R, Moore JD, Murray JB, et al. Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: protein structure-guided design and SAR. Bioorg Med Chem Lett. 2006;16(5):1353–1357.
  • Pistollato F, Rampazzo E, Abbadi S, Della Puppa A, Scienza R, D'Avella D, Denaro L, Te Kronnie G, Panchision DM, Basso G. Molecular mechanisms of HIF-1alpha modulation induced by oxygen tension and BMP2 in glioblastoma derived cells. PLOS One. 2009;4(7):e6206.
  • Pistollato F, Abbadi S, Rampazzo E, Persano L, Della Puppa A, Frasson C, Sarto E, Scienza R, D'Avella D, Basso G. Intratumoral hypoxic gradient drives stem cells distribution and MGMT expression in glioblastoma. Stem Cells. 2010;28(5):851–862.
  • Romagnoli R, Baraldi PG, Prencipe F, Oliva P, Baraldi S, Salvador MK, Lopez-Cara LC, Brancale A, Ferla S, Hamel E, et al. Synthesis and biological evaluation of 2-methyl-4,5-disubstituted oxazoles as a novel class of highly potent antitubulin agents. Sci Rep. 2017;7(1):46356.
  • Khalifah RG. The carbon dioxide hydration activity of carbonic anhydrase. I. Stop flow kinetic studies on the native human isoenzymes B and C. J Biol Chem. 1971;246(8):2561–2573.
  • Pastorekova S, Gillies RJ. The role of carbonic anhydrase IX in cancer development: links to hypoxia, acidosis, and beyond. Cancer Metastasis Rev. 2019;38(1–2):65–77.