A simple yet multifaceted 90 years old, evergreen enzyme: Carbonic anhydrase, its inhibition and activation

Bioorganic & Medicinal Chemistry Letters, Journal Year: 2023, Volume and Issue: 93, P. 129411 - 129411

Published: July 27, 2023

Language: Английский

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Carbonic anhydrase IX: An atypical target for innovative therapies in cancer

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(4), P. 189120 - 189120

Published: May 25, 2024

Carbonic anhydrases (CAs), are metallo-enzymes implicated in several pathophysiological processes where tissue pH regulation is required. CA IX a tumor-associated isoform induced by hypoxia and involved the adaptation of tumor cells to acidosis. Indeed, tumor-driving pathways can induce expression, this turn has been associated cancer invasion metastatic features as well induction stem-like features, drug resistance recurrence. After its functional structural characterization targeting approaches have developed inhibit activity neoplastic tissues, date field seen an incredible acceleration terms therapeutic options biological readouts. Small molecules inhibitors, hybrid/dual drugs, antibodies adoptive (CAR-T based) cell therapy at preclinical level, whereas sulfonamide inhibitor antibody entered Phase Ib/II clinical trials for treatment imaging different solid tumors. Here recent advances on biology pharmacology cancer, will be discussed.

Language: Английский

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A new framework for novel analogues of pazopanib as potent and selective human carbonic anhydrase inhibitors: Design, repurposing rational, synthesis, crystallographic, in vivo and in vitro biological assessments

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 274, P. 116527 - 116527

Published: May 24, 2024

Language: Английский

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Multi- and poly-pharmacology of carbonic anhydrase inhibitors

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 77(1), P. 100004 - 100004

Published: Sept. 26, 2024

Eight genetically distinct families of the enzyme carbonic anhydrase (CA, EC 4.2.1.1) have been described in organisms overall phylogenetic tree. They catalyze hydration CO2 to bicarbonate and protons are involved pH regulation, chemosensing, metabolism. The 15 α-CA isoforms present humans pharmacological drug targets known for decades, their inhibitors being used as diuretics, antiglaucoma, antiepileptic, or antiobesity drugs, well management acute mountain sickness, idiopathic intracranial hypertension, recently, antitumor theragnostic agents. Other potential applications include use CA (CAIs) inflammatory conditions, cerebral ischemia, neuropathic pain, Alzheimer/Parkinson disease management. CAs from pathogenic bacteria, fungi, protozoans, nematodes started be considered recent years, with notable advances registered. CAIs a complex multipharmacology probably unique this enzyme, which has exploited intensely but may lead other relevant future due emergence design approaches that afforded highly isoform-selective compounds most α-CAs date. belong multitude chemical classes (sulfonamides isosteres, [iso]coumarins related compounds, mono- dithiocarbamates, selenols, ninhydrines, boronic acids, benzoxaboroles, etc). polypharmacology will also discussed because drugs originally discovered treatment non-CA conditions (topiramate, zonisamide, celecoxib, pazopanib, thiazide, high-ceiling diuretics) show effective inhibition against many CAs, led repurposing diverse applications. SIGNIFICANCE STATEMENT: multiple pharmacologic applications, such antiobesity, antiacute anti-idiopathic drugs. Their neurodegenerations investigated recently. Parasite anhydrases anti-infectives novel mechanisms action can bypass resistance commonly Drugs effectively inhibit these enzymes exert interesting polypharmacologic effects.

Language: Английский

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Carbonic anhydrase inhibitors: Structural insights and therapeutic potential

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108224 - 108224

Published: Jan. 1, 2025

Language: Английский

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Targeting carbonic anhydrases for the management of hypoxic metastatic tumors

Expert Opinion on Therapeutic Patents, Journal Year: 2023, Volume and Issue: 33(11), P. 701 - 720

Published: Aug. 7, 2023

ABSTRACTIntroduction Several isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) are connected with tumorigenesis. Hypoxic tumors overexpress CA IX and XII as a consequence HIF activation cascade, being involved in pH regulation, metabolism, metastases formation. Other (CA I, II, III, IV) were also reported to be present some tumors.Areas Covered Some biomarkers for disease progression or response therapy. Inhibitors, antibodies, other procedures targeting these enzymes treatment tumors/metastases discussed. Sulfonamides coumarins represent most investigated classes inhibitors, but carboxylates, selenium, tellurium-containing inhibitors investigated. Hybrid drugs antitumor agents multitargeted therapy reported.Expert opinion Targeting CAs solid hematological selective, targeted is validated approach, which has been consolidated last years. A host new preclinical data several clinical trials antibodies small-molecule ongoing, large number chemotypes/procedures discovered effective, may lead breakthrough this therapeutic area. The scientific/patent literature searched on PubMed, ScienceDirect, Espacenet, PatentGuru, from 2018 2023.KEYWORDS: anhydraseanticancer drugshypoxic tumorinhibitorssulfonamidescoumarinsantibodieshybrid Article highlights hCA expressed hypoxic tumor cells, promoting growth metastasis formation tumorsIsoforms such IV found many types, considered novel targetsExosomes patients enriched cancer-associated CAs, IXA available, chemotypes periodSulfonamides prevalently isoform-selective compounds available dateNovel chemotypes, incorporating selenium tellurium obtained, contribute effects by additional mechanisms actionHybrid (estrogen receptor modulators; vascular endothelial factor 2 antagonists; H2S releasing agents; signal transducer transcriptional activator 3 mono- triterpenes) possess enhanced antitumor/antimetastatic effectsSeveral MAbs one sulfonamide inhibitor (SLC-0111) under evaluation various phases development.Declaration interestsClaudiu T Supuran declares conflict interest discoverer SLC-0111 phase Ib/II trials. author no relevant affiliations financial involvement any organization entity subject matter materials discussed manuscript apart those disclosed.Reviewer disclosuresPeer reviewers have relationships disclose.Additional informationFundingThis paper was not funded.

Language: Английский

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Antibody-drug conjugates and radioconjugates targeting carbonic anhydrase IX and XII in hypoxic tumors: Bench to clinical applications

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108408 - 108408

Published: March 1, 2025

Language: Английский

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Recent Advances in Photoswitchable Fluorescent and Colorimetric Probes

Molecules, Journal Year: 2024, Volume and Issue: 29(11), P. 2521 - 2521

Published: May 27, 2024

In recent years, significant advancements have been made in the research of photoswitchable probes. These probes undergo reversible structural and electronic changes upon light exposure, thus exhibiting vast potential molecular detection, biological imaging, material science, information storage. Through precisely engineered structures, can toggle between “on” “off” states at specific wavelengths, enabling highly sensitive selective detection targeted analytes. This review systematically presents fluorescent colorimetric built on various photoswitches, primarily focusing types involving photoswitching their and/or signal response processes. It begins with an analysis including photophysical properties, photoisomerization photochromic mechanisms, fundamental design concepts for constructing The article then elaborates applications these detecting diverse targets, cations, anions, small molecules, biomacromolecules. Finally, it offers perspectives current state future development aims to provide a clear introduction researchers field guidance application new, efficient

Language: Английский

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Simultaneous visualization of lipid droplets and tracking of the endogenous hypochlorous acid in psoriatic mice models with a novel fluorescent probe in a wash-free fashion

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 153, P. 107967 - 107967

Published: Nov. 16, 2024

Language: Английский

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Synthesis, biological evaluation and molecular docking studies of novel 1,3,4-thiadiazoles as potential anticancer agents and human carbonic anhydrase inhibitors

Molecular Diversity, Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 20, 2023

Language: Английский

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