a Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Adiyaman University , Adiyaman , Turkey.
b NEUROFARBA Dept., Sezione di Scienze Farmaceutiche , Università degli Studi di Firenze , Sesto Fiorentino (Florence) , Italy.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):1575-1580. doi: 10.1080/14756366.2018.1515933.
A series of new 1,3-diaryltriazene sulfonamides was synthesised by reaction of diazonium salt of metanilamide (3-aminobenzene sulfonamide) with substituted aromatic amines. The obtained new compounds were assayed as inhibitors of four physiologically and pharmacologically relevant human (h) isoforms of carbonic anhydrases (CA, EC 4.2.1.1), specifically, hCA I, hCA II, and hCA VII (cytosolic isoforms), as well as the tumour-associated membrane-bound isoform hCA IX. All isoforms investigated here were inhibited by the newly synthesised 1,3-diaryltriazene sulfonamide derivatives from the micromolar to the nanomolar range. The cytosolic isoforms were inhibited with Ks in the range of 92.3-8371.1 nM (hCA I), 4.3-9194.0 nM (hCA II), and 15.6-9477.8 nM (hCA VII), respectively. For the membrane-bound tumour-associated isoform hCA IX, the K ranged between 50.8 and 9268.5 nM. The structure-activity relationship (SAR) with these newly synthesised metanilamide derivatives are discussed in detail.
一系列新的 1,3-二芳基三嗪磺酰胺是通过米他胺（3-氨基苯磺酰胺）的重氮盐与取代的芳族胺反应合成的。所得到的新化合物被用作四种生理上和药理学上相关的人（h）碳酸酐酶（CA，EC 4.2.1.1）同工酶的抑制剂，特别是 hCA I、hCA II 和 hCA VII（胞质同工酶），以及肿瘤相关的膜结合同工酶 hCA IX。所有在此研究的同工酶都被新合成的 1,3-二芳基三嗪磺酰胺衍生物在微摩尔至纳摩尔范围内抑制。胞质同工酶的抑制常数（Ki）范围分别为 92.3-8371.1 nM（hCA I）、4.3-9194.0 nM（hCA II）和 15.6-9477.8 nM（hCA VII）。对于膜结合的肿瘤相关同工酶 hCA IX，Ki 值在 50.8 和 9268.5 nM 之间。详细讨论了这些新合成的米他胺衍生物的构效关系（SAR）。
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