Kumar Rajiv, Sharma Vikas, Bua Silvia, Supuran Claudiu T, Sharma Pawan K
a Department of Chemistry , Kurukshetra University , Kurukshetra , India.
b Neurofarba Department, Laboratorio di Chimica Bioinorganica, Sezione di Scienze Farmaceutiche , Università degli Studi di Firenze , Firenze , Italy.
J Enzyme Inhib Med Chem. 2017 Dec;32(1):1187-1194. doi: 10.1080/14756366.2017.1367775.
A library of benzenesulphonamides incorporating 1,2,3-triazole rings functionalised with ester, carboxylic acid, carboxamide, carboxyhydrazide, and hydroxymethyl moieties were synthesised. The carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA IV, and hCA IX. Among them, hCA II and IV are anti-glaucoma drug targets, being involved in aqueous humour secretion within the eye. hCA I was inhibited with Ki's ranging between 8.3 nM and 0.8737 µM. hCA II, the physiologically dominant cytosolic isoform, was excellently inhibited by these compounds, with Ki's in the range of 1.6-9.4 nM, whereas hCA IV was effectively inhibited by most of them, with Ki's in the range of 1.4-55.3 nM. Thirteen of the twenty sulphonamides were found to be excellent inhibitors of tumour associated hCA IX with Ki's ≤ 9.5 nM. Many of the new compounds reported here showed low nM inhibitory action against hCA II, IV, and IX, isoforms involved in glaucoma and some tumours, making them interesting candidates for further medicinal chemistry/pharmacologic studies.
合成了一系列含有经酯、羧酸、羧酰胺、羧基酰肼和羟甲基部分官能化的1,2,3 - 三唑环的苯磺酰胺库。评估了新化合物对四种人（h）同工型，即hCA I、hCA II、hCA IV和hCA IX的碳酸酐酶（CAs，EC 4.2.1.1）抑制活性。其中，hCA II和IV是抗青光眼药物靶点，参与眼内房水分泌。hCA I的抑制常数（Ki）在8.3 nM至0.8737 μM之间。生理上占主导地位的胞质同工型hCA II被这些化合物出色地抑制，Ki在1.6 - 9.4 nM范围内，而hCA IV被其中大多数有效抑制，Ki在1.4 - 55.3 nM范围内。发现二十种磺酰胺中的十三种是肿瘤相关hCA IX的出色抑制剂，Ki≤9.5 nM。本文报道的许多新化合物对参与青光眼和一些肿瘤的hCA II、IV和IX同工型表现出低纳摩尔抑制作用，使其成为进一步药物化学/药理学研究的有趣候选物。
