Screening Campaign and Docking Investigations in Identifying New Hit Compounds as Inhibitors of Human Carbonic Anhydrases Expressed In Tumour Cells.
Humans
Structure-Activity Relationship
Carbonic Anhydrases
/ metabolism
Carbonic Anhydrase IX
/ metabolism
Antigens, Neoplasm
/ metabolism
Carbonic Anhydrase I
/ metabolism
Neoplasms
/ drug therapy
Protein Isoforms
/ metabolism
Carbonic Anhydrase Inhibitors
/ chemistry
Molecular Structure
Tumor Microenvironment
antitumor agents
arylsulfonamides
carbonic anhydrase
docking studies
molecular modeling
Journal
ChemMedChem
ISSN: 1860-7187
Titre abrégé: ChemMedChem
Pays: Germany
ID NLM: 101259013
Informations de publication
Date de publication:
17 10 2023
17 10 2023
Historique:
revised:
06
09
2023
received:
28
06
2023
medline:
31
10
2023
pubmed:
11
9
2023
entrez:
11
9
2023
Statut:
ppublish
Résumé
The tumor-expressed human carbonic anhydrase (hCA) isoforms hCA IX and hCA XII have been extensively studied to develop anticancer agents targeting solid tumors in combined therapy. These CA isoforms are considered key factors in controlling tumor microenvironment (TME) of cancer lines that develop high metastatic activity. Herein, we report the discovery of potent hCA IX/hCA XII inhibitors that were disclosed through a screening campaign on an in-house collection of arylsulfonamides preliminary tested toward other hCAs. Among them, the N-(4-sulfamoylphenyl)naphthalene-2-carboxamide (12) and N-(4-sulfamoylphenyl)-3,4-dihydroisoquinoline-2(1H)-carbothioamide (15) proved to be the most intriguing hCA IX/hCA XII inhibitors displaying favourable selectivity ratios over widespread hCA I and hCA II isoforms. To explore their binding mode, we conducted docking studies that described the poses of the best inhibitors in the catalytic site of hCA IX and hCA XII, thus suggesting the privileged pattern of interactions. These structural findings might further improve the knowledge for a successful identification of new sulfonamides as adjuvant agents in cancer management.
Identifiants
pubmed: 37694943
doi: 10.1002/cmdc.202300330
doi:
Substances chimiques
Carbonic Anhydrases
EC 4.2.1.1
Carbonic Anhydrase IX
EC 4.2.1.1
Antigens, Neoplasm
0
Carbonic Anhydrase I
EC 4.2.1.-
Protein Isoforms
0
Carbonic Anhydrase Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202300330Informations de copyright
© 2023 The Authors. ChemMedChem published by Wiley-VCH GmbH.
Références
A. Aspatwar, M. E. E. Tolvanen, H. Barker, L. Syrjanen, S. Valanne, S. Purmonen, A. Waheed, W. S. Sly, S. Parkkila, Physiol. Rev. 2022, 102, 1327-1383.
C. T. Supuran, Expert Opin. Drug Metab. Toxicol. 2020, 16, 297-307.
C. T. Supuran, Expert Opin. Drug Discovery 2020, 15, 671-686.
A. Nocentini, C. T. Supuran, Expert Opin. Drug Discovery 2019, 14, 1175-1197.
F. Mancuso, A. Di Fiore, L. De Luca, A. Angeli, S. M. Monti, G. De Simone, C. T. Supuran, R. Gitto, ACS Med. Chem. Lett. 2020, 11, 1000-1005.
T. Koltai, Cancer Drug Resist 2022, 5, 277-303.
N. S. P. Campos, B. S. Souza, G. Silva, V. A. Porto, G. M. Chalbatani, G. Lagreca, B. Janji, E. R. Suarez, Cancers (Basel) 2022, 14.
A. Kumar, K. Siwach, C. T. Supuran, P. K. Sharma, Bioorg. Chem. 2022, 126, 105920.
K. F. Tonissen, S. A. Poulsen, Cancer Drug Resist 2021, 4, 343-355.
A. Dorbabu, Arch. Pharm. 2023, 356, e2200562.
J. N. Ivanova, A. Nocentini, K. Ta Rs, J. N. Leita Ns, E. Dvinskis, A. Kazaks, I. Domraceva, C. T. Supuran, R. Zalubovskis, J. Med. Chem. 2023, 66, 5703-5718.
J. Combs, M. Bozdag, L. D. Cravey, A. Kota, R. McKenna, A. Angeli, F. Carta, C. T. Supuran, Molecules 2023, 28.
A. Bonardi, S. Bua, J. Combs, C. Lomelino, J. Andring, S. M. Osman, A. Toti, L. Di Cesare Mannelli, P. Gratteri, C. Ghelardini, R. McKenna, A. Nocentini, C. T. Supuran, J. Enzyme Inhib. Med. Chem. 2022, 37, 930-939.
J. T. Andring, M. Fouch, S. Akocak, A. Angeli, C. T. Supuran, M. A. Ilies, R. McKenna, J. Med. Chem. 2020, 63, 13064-13075.
L. De Luca, A. Angeli, F. Ricci, C. T. Supuran, R. Gitto, Arch. Pharm. 2023, 356, e2200383.
F. Mancuso, L. De Luca, F. Bucolo, M. Vrabel, A. Angeli, C. Capasso, C. T. Supuran, R. Gitto, ChemMedChem 2021, 16, 3787-3794.
F. Pacchiano, F. Carta, P. C. McDonald, Y. Lou, D. Vullo, A. Scozzafava, S. Dedhar, C. T. Supuran, J. Med. Chem. 2011, 54, 1896-1902.
R. Gitto, S. Agnello, S. Ferro, L. De Luca, D. Vullo, J. Brynda, P. Mader, C. T. Supuran, A. Chimirri, J. Med. Chem. 2010, 53, 2401-2408.
A. Pedretti, A. Mazzolari, S. Gervasoni, L. Fumagalli, G. Vistoli, Bioinformatics 2021, 37, 1174-1175.
G. Jones, P. Willett, R. C. Glen, A. R. Leach, R. Taylor, J. Mol. Biol. 1997, 267, 727-748.
G. Wolber, T. Langer, J. Chem. Inf. Model. 2005, 45, 160-169.