: Here, we report for the first time a series of sulfonamide derivatives with scaffolds bearing flexible moieties, namely, rotamers or tropoisomers capable of adapting their geometry in the active center of enzymes thus being effective and selective carbonic anhydrase (CAs, EC 4.2.1.1) enzyme inhibitors. All compounds exhibited effective in vitro inhibition activity toward the main hCA isoforms related to cancer (i.e., hCA II, hCA IX, and hCA XII with KI values in the low nanomolar range). Three selected compounds showed a great cytotoxic effect on cancer cell lines ex vivo. X-ray crystallographic experiments assessed the binding modes of compound 35 with active centers of hCA IX and hCA XII.
Atropo/Tropo Flexibility: A Tool for Design and Synthesis of Self-Adaptable Inhibitors of Carbonic Anhydrases and Their Antiproliferative Effect / Ivanova, Jekateri Na; Nocentini, Alessio; Ta Rs, Kaspars; Leita Ns, Ja Nis; Dvinskis, Elviss; Kazaks, Andris; Domračeva, Ilona; Supuran, Claudiu T; Žalubovskis, Raivis. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 1520-4804. - ELETTRONICO. - 66:(2023), pp. 0-0. [10.1021/acs.jmedchem.3c00007]
Atropo/Tropo Flexibility: A Tool for Design and Synthesis of Self-Adaptable Inhibitors of Carbonic Anhydrases and Their Antiproliferative Effect
Nocentini, Alessio;Supuran, Claudiu T;
2023
Abstract
: Here, we report for the first time a series of sulfonamide derivatives with scaffolds bearing flexible moieties, namely, rotamers or tropoisomers capable of adapting their geometry in the active center of enzymes thus being effective and selective carbonic anhydrase (CAs, EC 4.2.1.1) enzyme inhibitors. All compounds exhibited effective in vitro inhibition activity toward the main hCA isoforms related to cancer (i.e., hCA II, hCA IX, and hCA XII with KI values in the low nanomolar range). Three selected compounds showed a great cytotoxic effect on cancer cell lines ex vivo. X-ray crystallographic experiments assessed the binding modes of compound 35 with active centers of hCA IX and hCA XII.I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.