Tumor associated carbonic anhydrase inhibitors: Rational approaches, design strategies, structure activity relationship and mechanistic insights
The emergence of tumor-associated human carbonic anhydrases (hCA) as promising therapeutic targets has urged rigorous research into the development of potent and selective hCA IX and XII inhibitors. Rationalization of targeting tumor-specific hCA isoforms is a major challenge that requires a compreh...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | European Journal of Medicinal Chemistry Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772417424000037 |
| _version_ | 1827318524534587392 |
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| author | Sridhar Goud Nerella Pavitra S. Thacker Mohammed Arifuddin Claudiu T. Supuran |
| author_facet | Sridhar Goud Nerella Pavitra S. Thacker Mohammed Arifuddin Claudiu T. Supuran |
| author_sort | Sridhar Goud Nerella |
| collection | DOAJ |
| description | The emergence of tumor-associated human carbonic anhydrases (hCA) as promising therapeutic targets has urged rigorous research into the development of potent and selective hCA IX and XII inhibitors. Rationalization of targeting tumor-specific hCA isoforms is a major challenge that requires a comprehensive understanding of the interactions between inhibitors and the dynamic hCA active site. The benzenesulfonamides and its bioisosteres are currently being used clinically as inhibitors of various hCA isoforms through classical inhibitory mechanism. In addition, several other chemotypes have also been developed with improved potency and selectivity through non-classical inhibitory mechanisms. Coumarin and its derivatives represent highly selective and potent inhibitors of hCA IX and XII. Recently, various other pharmacophores were also proven to have a strong selectivity and potency against hCA IX and XII including pyrazole, 1,2,3-triazole, 4-thiazolidinone, and thiourea. This review navigates through understanding the role of hCA IX and XII in cancer biology, encompassing different inhibition approaches, strategic design methodologies, recent advancements in the rational design of hCA inhibitors, exploration of structure-activity relationships, in-depth mechanistic insights, and PET imaging applications for in vivo visualization of target enzymes. |
| first_indexed | 2024-03-08T12:47:13Z |
| format | Article |
| id | doaj.art-440b5e869c2645aea2ef76e818f8843b |
| institution | Directory Open Access Journal |
| issn | 2772-4174 |
| language | English |
| last_indexed | 2024-04-25T00:02:31Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Medicinal Chemistry Reports |
| spelling | doaj.art-440b5e869c2645aea2ef76e818f8843b2024-03-14T06:17:04ZengElsevierEuropean Journal of Medicinal Chemistry Reports2772-41742024-04-0110100131Tumor associated carbonic anhydrase inhibitors: Rational approaches, design strategies, structure activity relationship and mechanistic insightsSridhar Goud Nerella0Pavitra S. Thacker1Mohammed Arifuddin2Claudiu T. Supuran3Department of Neuroimaging and Interventional Radiology (NI & IR), National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, 560 029, India; Corresponding author.Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500 037, IndiaDepartment of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500 037, India; Department of Chemistry, Directorate of Distance Education, Maulana Azad National Urdu University, Hyderabad, IndiaUniversità degli Studi di Firenze, Neurofarba Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019, Sesto Fiorentino, Florence, Italy; Corresponding author.The emergence of tumor-associated human carbonic anhydrases (hCA) as promising therapeutic targets has urged rigorous research into the development of potent and selective hCA IX and XII inhibitors. Rationalization of targeting tumor-specific hCA isoforms is a major challenge that requires a comprehensive understanding of the interactions between inhibitors and the dynamic hCA active site. The benzenesulfonamides and its bioisosteres are currently being used clinically as inhibitors of various hCA isoforms through classical inhibitory mechanism. In addition, several other chemotypes have also been developed with improved potency and selectivity through non-classical inhibitory mechanisms. Coumarin and its derivatives represent highly selective and potent inhibitors of hCA IX and XII. Recently, various other pharmacophores were also proven to have a strong selectivity and potency against hCA IX and XII including pyrazole, 1,2,3-triazole, 4-thiazolidinone, and thiourea. This review navigates through understanding the role of hCA IX and XII in cancer biology, encompassing different inhibition approaches, strategic design methodologies, recent advancements in the rational design of hCA inhibitors, exploration of structure-activity relationships, in-depth mechanistic insights, and PET imaging applications for in vivo visualization of target enzymes.http://www.sciencedirect.com/science/article/pii/S2772417424000037Human carbonic anhydraseshCA IXhCA XIICancerAnticancer agents |
| spellingShingle | Sridhar Goud Nerella Pavitra S. Thacker Mohammed Arifuddin Claudiu T. Supuran Tumor associated carbonic anhydrase inhibitors: Rational approaches, design strategies, structure activity relationship and mechanistic insights European Journal of Medicinal Chemistry Reports Human carbonic anhydrases hCA IX hCA XII Cancer Anticancer agents |
| title | Tumor associated carbonic anhydrase inhibitors: Rational approaches, design strategies, structure activity relationship and mechanistic insights |
| title_full | Tumor associated carbonic anhydrase inhibitors: Rational approaches, design strategies, structure activity relationship and mechanistic insights |
| title_fullStr | Tumor associated carbonic anhydrase inhibitors: Rational approaches, design strategies, structure activity relationship and mechanistic insights |
| title_full_unstemmed | Tumor associated carbonic anhydrase inhibitors: Rational approaches, design strategies, structure activity relationship and mechanistic insights |
| title_short | Tumor associated carbonic anhydrase inhibitors: Rational approaches, design strategies, structure activity relationship and mechanistic insights |
| title_sort | tumor associated carbonic anhydrase inhibitors rational approaches design strategies structure activity relationship and mechanistic insights |
| topic | Human carbonic anhydrases hCA IX hCA XII Cancer Anticancer agents |
| url | http://www.sciencedirect.com/science/article/pii/S2772417424000037 |
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