Sultam based Carbonic Anhydrase VII inhibitors for the management of neuropathic pain(59 views) Akgül Ö, Lucarini E, Mannelli LDC, Ghelardini C, D'Xambrosio K, Buonanno M, Monti SM, De Simone G, Angeli A, Supuran CT, Carta F
Eur J Med Chem (ISSN: 0223-5234linking, 1768-3254, 1768-3254electronic), 2022 Jan 5; 227: 113956-113956.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ege University, 35100, Bornova, İzmir, Turkey., NEUROFARBA Department, Section of Pharmacology and Toxicology, Università degli Studi di Firenze, Viale Pieraccini 6, 50139, Florence, Italy., Institute of Biostructures and Bioimaging, CNR, via Mezzocannone 16, 80134, Naples, Italy., Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019, Sesto Fiorentino (Florence), Italy., Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019, Sesto Fiorentino (Florence), Italy. Electronic address: fabrizio.carta@unifi.it.,
References: Not available.
Sultam based Carbonic Anhydrase VII inhibitors for the management of neuropathic pain
We report a series of compounds 1-17 derived from the antiepileptic drug Sulthiame (SLT) from which both the benzenesulfonamide and the sultam moiety were retained. All compounds were tested in vitro for their inhibition activity against the human (h) Carbonic Anhydrase (CA; EC 4.2.1.1) I, II, VII, IX and XII isoforms. Among the series, derivatives 1 and 11 showed great enhancement of both inhibition potency and selectivity towards the hCA VII isoform, when compared to the reference SLT drug. The binding mode of 11 within the hCA VII active site was deciphered by means of X-ray crystallography and revealed the sultam moiety being exposed to the rim of the active site. In vivo experiments on a model of neuropathic pain induced by oxaliplatin clearly showed 11 being an effective pain relieving agent and therefore worth of further exploitation towards the validation of the hCA VII as new target for the management of neuropathies.
Sultam based Carbonic Anhydrase VII inhibitors for the management of neuropathic pain
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