Design, synthesis and biological activity of selective hCAs inhibitors based on 2-(benzylsulfinyl)benzoic acid scaffold

被引：23

作者：

Rotondi, Giulia ^{[1
]}

Guglielmi, Paolo ^{[1
]}

Carradori, Simone ^{[2
]}

Secci, Daniela ^{[1
]}

De Monte, Celeste ^{[1
]}

De Filippis, Barbara ^{[2
]}

Maccallini, Cristina ^{[2
]}

Amoroso, Rosa ^{[2
]}

Cirilli, Roberto ^{[3
]}

Akdemir, Atilla ^{[4
]}

Angeli, Andrea ^{[5
]}

Supuran, Claudiu T. ^{[5
]}

机构：

[1] Sapienza Univ Rome, Dipartimento Chim & Tecnol Farmaco, Ple A Moro 5, I-00185 Rome, Italy

[2] G DAnnunzio Univ Chieti Pescara, Dept Pharm, Chieti, Italy

[3] Ist Super Sanita, Ctr Nazl Controllo & Valutaz Farm, Rome, Italy

[4] Bezmialem Vakif Univ, Dept Pharmacol, Fac Pharm, Comp Aided Drug Discovery Lab, Istanbul, Turkey

[5] Univ Firenze, Sect Pharmaceut & Nutraceut Sci, Neurofarba Dept, Via U Schiff 6, I-50019 Florence, Italy

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2019年 / 34卷 / 01期

关键词：

Carbonic anhydrase inhibitor; sulfoxide enantioseparation; carboxylic acid; molecular modelling; CARBONIC-ANHYDRASE-IX; FASCINATING MOLECULAR FRAMEWORK; ENANTIOSEPARATION ABILITY; SULFONAMIDE DERIVATIVES; DRUG DISCOVERY; CANCER; PH; 3-(PHENYL-4-OXY)-5-PHENYL-4,5-DIHYDRO-(1H)-PYRAZOLE; ENANTIOMERS; ASSIGNMENT;

D O I：

10.1080/14756366.2019.1651315

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 large library of derivatives based on the scaffold of 2-(benzylsulfinyl)benzoic acid were synthesised and tested as atypical inhibitors against four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). The exploration of the chemical space around the main functional groups led to the discovery of selective hCA IX inhibitors in the micromolar/nanomolar range, thus establishing robust structure-activity relationships within this versatile scaffold. HPLC separation of some selected chiral compounds and biological evaluation of the corresponding enantiomers was performed along with molecular modelling studies on the most active derivatives.

引用

页码：1400 / 1413

页数：14

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