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Reviews

Anti-obesity carbonic anhydrase inhibitors: challenges and opportunities

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Pages 2478-2488 | Received 03 Aug 2022, Accepted 31 Aug 2022, Published online: 08 Sep 2022

References

  • Müller TD, Blüher M, Tschöp MH, DiMarchi RD. Anti-obesity drug discovery: advances and challenges. Nat Rev Drug Discov 2022;21:201–23.
  • Batchuluun B, Pinkosky SL, Steinberg GR. Lipogenesis inhibitors: therapeutic opportunities and challenges. Nat Rev Drug Discov 2022;21:283–305.
  • Burki T. European Commission classifies obesity as a chronic disease. Lancet Diabetes Endocrinol 2021;9:418.
  • de Luis D, Primo D, Izaola O, Aller R. A pilot study of gene expression analysis in peripheral blood mononuclear cells in response to a hypocaloric mediterranean diet. Dis Markers 2022;2022:3706753.
  • Redmond IP, Shukla AP, Aronne LJ. Use of weight loss medications in patients after bariatric surgery. Curr Obes Rep 2021;10:81–9.
  • Czepiel KS, Perez NP, Campoverde Reyes KJ, et al. Pharmacotherapy for the treatment of overweight and obesity in children, adolescents, and young adults in a large health system in the US. Front Endocrinol (Lausanne) 2020;11:290.
  • Supuran CT. Emerging role of carbonic anhydrase inhibitors. Clin Sci 2021;135:1233–49.
  • De Simone G, Supuran CT. Antiobesity carbonic anhydrase inhibitors. Curr Top Med Chem 2007;7:879–84.
  • De Simone G, Di Fiore A, Supuran CT. Are carbonic anhydrase inhibitors suitable for obtaining antiobesity drugs? Curr Pharm Des 2008;14:655–60.
  • Supuran CT, Di Fiore A, De Simone G. Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs 2008;13:383–92.
  • Supuran CT. Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs 2012;17:11–5.
  • Scozzafava A, Supuran CT, Carta F. Antiobesity carbonic anhydrase inhibitors: a literature and patent review. Expert Opin Ther Pat 2013;23:725–35.
  • Supuran CT. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat Rev Drug Discov 2008;7:168–81.
  • Supuran CT. Advances in structure-based drug discovery of carbonic anhydrase inhibitors. Expert Opin Drug Discov 2017;12:61–88.
  • Aspatwar A, Tolvanen MEE, Barker H, et al. Carbonic anhydrases in metazoan model organisms: molecules, mechanisms, and physiology. Physiol Rev 2022;102:1327–83.
  • Supuran CT. Carbonic anhydrases and metabolism. Metabolites 2018;8:25.
  • a) Angeli A, Carta F, Nocentini A, et al. Carbonic anhydrase inhibitors targeting metabolism and tumor microenvironment. Metabolites 2020;10:412. b) Nocentini A, Angeli A, Carta F, et al. Reconsidering anion inhibitors in the general context of drug design studies of modulators of activity of the classical enzyme carbonic anhydrase. J Enzyme Inhib Med Chem 2021;36:561–80.
  • Supuran CT. Experimental carbonic anhydrase inhibitors for the treatment of hypoxic tumors. J Exp Pharmacol 2020;12:603–17.
  • Nishimori I, Vullo D, Innocenti A, et al. Carbonic anhydrase inhibitors. The mitochondrial isozyme VB as a new target for sulfonamide and sulfamate inhibitors. J Med Chem 2005;48:7860–6.
  • Bernardino RL, Dias TR, Moreira BP, et al. Carbonic anhydrases are involved in mitochondrial biogenesis and control the production of lactate by human Sertoli cells. Febs J 2019;286:1393–406.
  • Lynch CJ, Fox H, Hazen SA, et al. Role of hepatic carbonic anhydrase in de novo lipogenesis. Biochem J 1995;310:197–202.
  • Chegwidden WR, Spencer IM. Carbonic anhydrase provides bicarbonate for de novo lipogenesis in the locus. Comp Biochem Physiol 1996;115:247–54.
  • Hazen SA, Waheed A, Sly WS, et al. Differentiation-dependent expression of CA V and the role of carbonic anhydrase isozymes in pyruvate carboxylation in adipocytes. Faseb J 1996;10:481–90.
  • Atwood PV. The structure and mechanism of action of pyruvate carboxylase. Int J Biochem Cell Biol 1995;27:231–49.
  • Alldred JB, Reilly KE. Short-term regulation of acetyl CoA carboxylase in tissues of higher animals. Prog Lipid Res 1997;35:371–85.
  • Arechederra RL, Waheed A, Sly WS, et al. Effect of sulfonamides as carbonic anhydrase VA and VB inhibitors on mitochondrial metabolic energy conversion. Bioorg Med Chem 2013;21:1544–8.
  • Antel J, Hebebrand J. Weight-reducing side effects of the antiepileptic agents topiramate and zonisamide. Handb Exp Pharmacol 2012;209:433–66.
  • Alver A, Uçar F, Keha EE, et al. Effects of leptin and insulin on CA III expression in rat adipose tissue. J Enzyme Inhib Med Chem 2004;19:279–81.
  • Yamamoto H, Uramaru N, Kawashima A, Higuchi T. Carbonic anhydrase 3 increases during liver adipogenesis even in pre-obesity, and its inhibitors reduce liver adipose accumulation. FEBS Open Bio 2022;12:827–34.
  • Liu D, Wong CC, Zhou Y, et al. Squalene epoxidase induces nonalcoholic steatohepatitis via binding to carbonic anhydrase III and is a therapeutic target. Gastroenterology 2021;160:2467–82.e3.
  • Renner SW, Walker LM, Forsberg LJ, et al. Carbonic anhydrase III (Car3) is not required for fatty acid synthesis and does not protect against high-fat diet induced obesity in mice. PLoS One 2017;12:e0176502.
  • Nishimori I, Minakuchi T, Onishi S, et al. Carbonic anhydrase inhibitors. Cloning, characterization and inhibition studies of the cytosolic isozyme III with anions. J Enzyme Inhib Med Chem 2009;24:70–6.
  • a) Supuran CT. Exploring the multiple binding modes of inhibitors to carbonic anhydrases for novel drug discovery. Expert Opin Drug Discov 2020;15:671–86. (b) 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.
  • Supuran CT, Capasso C. Antibacterial carbonic anhydrase inhibitors: an update on the recent literature. Expert Opin Ther Pat 2020;30:963–82.
  • Mincione F, Nocentini A, Supuran CT. Advances in the discovery of novel agents for the treatment of glaucoma. Expert Opin Drug Discov 2021;16:1209–25.
  • Shank RP, Gardocki JF, Vaught JL, et al. Topiramate: preclinical evaluation of structurally novel anticonvulsant. Epilepsia 1994;35:450–60.
  • Zareba G. Zonisamide: review of its use in epilepsy therapy. Drug Today 2005;41:589–97.
  • Picard F, Deshaies Y, Lalonde J, et al. Topiramate reduces energy and fat gains in lean (Fa/?) and obese (fa/fa) Zucker rats. Obesity Res 2000;8:656–63.
  • Klein KM, Theisen F, Knake S, et al. Topiramate, nutrition and weight change: a prospective study. J Neurol Neurosurg Psychiatry 2008;79:590–3.
  • Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet 2011;377:1341–52.
  • Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr 2012;95:297–308.
  • Gadde KM, Franciscy DM, Wagner HR, 2nd, Krishnan KR. Zonisamide for weight loss in obese adults: a randomized controlled trial. JAMA 2003;289:1820–5.
  • Gordon A, Price LH. Mood stabilization and weight loss with topiramate. Am J Psychiatry 1999;156:968–9.
  • Lévy E, Agbokou C, Ferreri F, et al. Topiramate-induced weight loss in schizophrenia: a retrospective case series study. Can J Clin Pharmacol 2007;14:e234–9.
  • Mahmood S, Booker I, Huang J, Coleman CI. Effect of topiramate on weight gain in patients receiving atypical antipsychotic agents. J Clin Psychopharmacol 2013;33:90–4.
  • Schneiderhan ME, Marvin R. Is acetazolamide similar to topiramate for reversal of antipsychotic-induced weight gain? Am J Ther 2007;14:581–4.
  • Muñoz W, Lamm A, Poppers D, Lamm S. Acetazolamide promotes decreased consumption of carbonated drinks and weight loss. Oxf Med Case Reports 2018;2018:omy081.
  • Wallingford NM, Sinnayah P, Bymaster FP, et al. Zonisamide prevents olanzapine-associated hyperphagia, weight gain, and elevated blood glucose in rats. Neuropsychopharmacology 2008;33:2922–33.
  • Aronne LJ, Wadden TA, Peterson C, et al. Evaluation of phentermine and topiramate versus phentermine/topiramate extended-release in obese adults. Obesity 2013;21:2163–71.
  • Sari C, Seip RL, Umashanker D. Case Report: Off Label Utilization of Topiramate and Metformin in Patients With BMI ≥50 kg/m2 Prior to Bariatric Surgery. Front Endocrinol 2021;12:588016.
  • Casini A, Antel J, Abbate F, et al. Carbonic anhydrase inhibitors: SAR and X-ray crystallographic study for the interaction of sugar sulfamates/sulfamides with isozymes I, II and IV. Bioorg Med Chem Lett 2003;13:841–5.
  • De Simone G, Di Fiore A, Menchise V, et al. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: solution and X-ray crystallographic studies. Bioorg Med Chem Lett 2005;15:2315–20.
  • Supuran CT. Structure and function of carbonic anhydrases. Biochem J 2016;473:2023–32.
  • Supuran CT. How many carbonic anhydrase inhibition mechanisms exist? J Enzyme Inhib Med Chem 2016;31:345–60.
  • Alterio V, Monti SM, Truppo E, et al. The first example of a significant active site conformational rearrangement in a carbonic anhydrase-inhibitor adduct: the carbonic anhydrase I-topiramate complex. Org Biomol Chem 2010;8:3528–33.
  • Winum JY, Temperini C, El Cheikh K, et al. Carbonic anhydrase inhibitors: clash with Ala65 as a means for designing inhibitors with low affinity for the ubiquitous isozyme II, exemplified by the crystal structure of the topiramate sulfamide analogue. J Med Chem 2006;49:7024–31.
  • Vitale RM, Pedone C, Amodeo P, et al. Carbonic anhydrase inhibitors: molecular modeling study for the interaction of zonisamide and topiramate with isozyme VA. Bioorg Med Chem 2007;15:4152–8.
  • Davis RA, Innocenti A, Poulsen SA, Supuran CT. Carbonic anhydrase inhibitors. Identification of selective inhibitors of the human mitochondrial isozymes VA and VB over the cytosolic isozymes I and II from a natural product-based phenolic library. Bioorg Med Chem 2010;18:14–8.
  • Gidaro MC, Alcaro F, Carradori S, et al. Eriocitrin and Apigenin as New Carbonic Anhydrase VA Inhibitors from a Virtual Screening of Calabrian Natural Products. Planta Med 2015;81:533–40.
  • a) D'Ambrosio K, Carradori S, Cesa S, et al. Catechols: a new class of carbonic anhydrase inhibitors. Chem Commun (Camb) 2020;56:13033–6. b) Mollica A, Locatelli M, Macedonio G, et al. Microwave-assisted extraction, HPLC analysis, and inhibitory effects on carbonic anhydrase I, II, VA, and VII isoforms of 14 blueberry Italian cultivars. J Enzyme Inhib Med Chem 2016;31:1–6.
  • Costa G, Gidaro MC, Vullo D, et al. Active Components of Essential Oils as Anti-Obesity Potential Drugs Investigated by in Silico Techniques. J Agric Food Chem 2016;64:5295–300.
  • Dick BL, Patel A, McCammon JA, Cohen SM. Effect of donor atom identity on metal-binding pharmacophore coordination. J Biol Inorg Chem 2017;22:605–13.
  • Costa G, Carta F, Ambrosio FA, et al. A computer-assisted discovery of novel potential anti-obesity compounds as selective carbonic anhydrase VA inhibitors. Eur J Med Chem 2019;181:111565.
  • Costa G, Artese A, Ortuso F, Alcaro S. From Homology Modeling to the Hit Identification and Drug Repurposing: A Structure-Based Approach in the Discovery of Novel Potential Anti-Obesity Compounds. Methods Mol Biol 2021;2266:263–77.
  • Mori M, Supuran CT. Acipimox inhibits human carbonic anhydrases. J Enzyme Inhib Med Chem 2022;37:672–9.
  • Scozzafava A, Menabuoni L, Mincione F, et al. Carbonic anhydrase inhibitors. Synthesis of water-soluble, topically effective, intraocular pressure-lowering aromatic/heterocyclic sulfonamides containing cationic or anionic moieties: is the tail more important than the ring? J Med Chem 1999;42:2641–50.
  • Alterio V, Di Fiore A, D'Ambrosio K, et al. Multiple binding modes of inhibitors to carbonic anhydrases: how to design specific drugs targeting 15 different isoforms? Chem Rev 2012;112:4421–68.
  • Vullo D, Franchi M, Gallori E, et al. Carbonic anhydrase inhibitors. Inhibition of mitochondrial isozyme V with aromatic and heterocyclic sulfonamides. J Med Chem 2004;47:1272–9.
  • Güzel O, Innocenti A, Scozzafava A, et al. Carbonic anhydrase inhibitors. Aromatic/heterocyclic sulfonamides incorporating phenacetyl, pyridylacetyl and thienylacetyl tails act as potent inhibitors of human mitochondrial isoforms VA and VB. Bioorg Med Chem 2009;17:4894–9.
  • Smaine FZ, Pacchiano F, Rami M, et al. Carbonic anhydrase inhibitors: 2-substituted-1,3,4-thiadiazole-5-sulfamides act as powerful and selective inhibitors of the mitochondrial isozymes VA and VB over the cytosolic and membrane-associated carbonic anhydrases I, II and IV. Bioorg Med Chem Lett 2008;18:6332–5.
  • Poli G, Bozdag M, Berrino E, et al. N-aryl-N'-ureido-O-sulfamates as potent and selective inhibitors of hCA VB over hCA VA: Deciphering the binding mode of new potential agents in mitochondrial dysfunctions. Bioorg Chem 2020;100:103896.
  • Maresca A, Supuran CT. (R)-/(S)-10-camphorsulfonyl-substituted aromatic/heterocyclic sulfonamides selectively inhibit mitochondrial over cytosolic carbonic anhydrases. Bioorg Med Chem Lett 2011;21:1334–7.
  • Poulsen SA, Wilkinson BL, Innocenti A, et al. Inhibition of human mitochondrial carbonic anhydrases VA and VB with para-(4-phenyltriazole-1-yl)-benzenesulfonamide derivatives. Bioorg Med Chem Lett 2008;18:4624–7.
  • Shah GN, Morofuji Y, Banks WA, Price TO. High glucose-induced mitochondrial respiration and reactive oxygen species in mouse cerebral pericytes is reversed by pharmacological inhibition of mitochondrial carbonic anhydrases: Implications for cerebral microvascular disease in diabetes. Biochem Biophys Res Commun 2013;440:354–8.
  • Salameh TS, Mortell WG, Logsdon AF, et al. Disruption of the hippocampal and hypothalamic blood-brain barrier in a diet-induced obese model of type II diabetes: prevention and treatment by the mitochondrial carbonic anhydrase inhibitor, topiramate. Fluids Barriers CNS 2019;16:1.
  • Mullard A. New hope for anti-obesity drugs. Nat Rev Drug Discov 2021;20:575.