Discovery of novel 1,3-diaryltriazene sulfonamides as carbonic anhydrase I, II, VII, and IX inhibitors

被引:45
作者
Akocak, Suleyman [1 ]
Lolak, Nabih [1 ]
Bua, Silvia [2 ]
Supuran, Claudiu T. [2 ]
机构
[1] Adiyaman Univ, Fac Pharm, Dept Pharmaceut Chem, TR-02040 Adiyaman, Turkey
[2] Univ Firenze, NEUROFARBA Dept, Sez Sci Farmaceut, Via Ugo Schiff 6, I-50019 Sesto Fiorentino, Florence, Italy
关键词
Carbonic anhydrase; inhibitors; triazene; isozymes; metanilamide; BIOLOGICAL EVALUATION; ISOZYME-II; SCHIFF-BASES; METAL-COMPLEXES; DRUG TARGETS; POTENT; AGENTS; DERIVATIVES; ACTIVATORS; PURIFICATION;
D O I
10.1080/14756366.2018.1515933
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 K(i)s 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 KI-s ranged between 50.8 and 9268.5 nM. The structure-activity relationship (SAR) with these newly synthesised metanilamide derivatives are discussed in detail.
引用
收藏
页码:1575 / 1580
页数:6
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