New dihydro-pyrrol-2-one compounds, featuring dual sulfonamide groups, were synthesized through a one-pot, three-component approach utilizing trifluoroacetic acid as a catalyst. Computational analysis using density functional theory (DFT) and condensed Fukui function explored the structure-reactivity relationship. Evaluation against human carbonic anhydrase isoforms (hCA I, II, IX, XII) revealed potent inhibition. The widely expressed cytosolic hCA I was inhibited across a range of concentrations (K-I 3.9-870.9 nM). hCA II, also cytosolic, exhibited good inhibition as well. Notably, all compounds effectively inhibited tumor-associated hCA IX (K-I 1.9-211.2 nM) and hCA XII (low nanomolar). Biological assessments on MCF7 cancer cells highlighted the compounds' ability, in conjunction with doxorubicin, to significantly impact tumor cell viability. These findings underscore the potential therapeutic relevance of the synthesized compounds in cancer treatment.

Synthetic Approaches to Novel Human Carbonic Anhydrase Isoform Inhibitors Based on Pyrrol-2-one Moiety / Al-Matarneh, Cristina M.; Pinteala, Mariana; Nicolescu, Alina; Silion, Mihaela; Mocci, Francesca; Puf, Razvan; Angeli, Andrea; Ferraroni, Marta; Supuran, Claudiu T.; Zara, Susi; Carradori, Simone; Paoletti, Niccolò; Bonardi, Alessandro; Gratteri, Paola. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 67:(2024), pp. 67.3018-67.3038. [10.1021/acs.jmedchem.3c02190]

Synthetic Approaches to Novel Human Carbonic Anhydrase Isoform Inhibitors Based on Pyrrol-2-one Moiety

Ferraroni, Marta;Supuran, Claudiu T.;Bonardi, Alessandro;Gratteri, Paola
2024

Abstract

New dihydro-pyrrol-2-one compounds, featuring dual sulfonamide groups, were synthesized through a one-pot, three-component approach utilizing trifluoroacetic acid as a catalyst. Computational analysis using density functional theory (DFT) and condensed Fukui function explored the structure-reactivity relationship. Evaluation against human carbonic anhydrase isoforms (hCA I, II, IX, XII) revealed potent inhibition. The widely expressed cytosolic hCA I was inhibited across a range of concentrations (K-I 3.9-870.9 nM). hCA II, also cytosolic, exhibited good inhibition as well. Notably, all compounds effectively inhibited tumor-associated hCA IX (K-I 1.9-211.2 nM) and hCA XII (low nanomolar). Biological assessments on MCF7 cancer cells highlighted the compounds' ability, in conjunction with doxorubicin, to significantly impact tumor cell viability. These findings underscore the potential therapeutic relevance of the synthesized compounds in cancer treatment.
2024
67
3018
3038
Goal 3: Good health and well-being
Al-Matarneh, Cristina M.; Pinteala, Mariana; Nicolescu, Alina; Silion, Mihaela; Mocci, Francesca; Puf, Razvan; Angeli, Andrea; Ferraroni, Marta; Supuran, Claudiu T.; Zara, Susi; Carradori, Simone; Paoletti, Niccolò; Bonardi, Alessandro; Gratteri, Paola
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1355332
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