NEUROFARBA Department, Sezione di Scienze Farmaceutiche, University of Florence, Sesto Fiorentino, Florence, Italy.
Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Florence, Italy.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2178430. doi: 10.1080/14756366.2023.2178430.
Carbonic anhydrases (CAs) are a zinc metalloenzymes that catalyse the reversible hydration of carbon dioxide to bicarbonate and proton, pivotal for a wide range of biological processes. CAs are involved in numerous pathologies and thus represent valuable drug targets in the treatments of several diseases such as glaucoma, obesity, tumour, neuropathic pain, cerebral ischaemia, or as antiinfectives. In the last two decades, several efforts have been made to achieve selective CA inhibitors (CAIs) employing different drug design approaches. However, -substitutions on primary sulphonamide groups still remain poorly investigated. Here, we reported for the first time the co-crystallisation of a -nitro sulphonamide derivative with human (h) CA II pointing out the binding site and mode of inhibition of this class of CAIs. The thorough comprehension of the ligand/target interaction might be valuable for a further CAI optimisation for achieving new potent and selective derivatives.
碳酸酐酶（CA）是一类锌金属酶，可催化二氧化碳的可逆水合反应生成碳酸氢根和质子，这对广泛的生物过程至关重要。CA 参与了许多病理过程，因此在治疗多种疾病方面具有重要的应用价值，如青光眼、肥胖症、肿瘤、神经病理性疼痛、脑缺血或抗感染等。在过去的二十年中，人们已经进行了多项努力，采用不同的药物设计方法来获得选择性碳酸酐酶抑制剂（CAI）。然而，对于主磺酰胺基上的取代基研究仍然很少。在这里，我们首次报道了 -硝基磺酰胺衍生物与人源（h）CA II 的共结晶，指出了该类 CAI 的结合位点和抑制模式。深入了解配体/靶标相互作用对于进一步优化 CAI 以获得新的有效和选择性衍生物可能具有重要意义。
