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


Journal

Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203

Informations de publication

Date de publication:
Dec 2019
Historique:
entrez: 13 8 2019
pubmed: 14 8 2019
medline: 27 8 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 31401897
doi: 10.1080/14756366.2019.1651315
pmc: PMC6713143
doi:

Substances chimiques

Carbonic Anhydrase Inhibitors 0
Isoenzymes 0
Benzoic Acid 8SKN0B0MIM
Carbonic Anhydrases EC 4.2.1.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1400-1413

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Auteurs

Giulia Rotondi (G)

a Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome , Rome , Italy.

Paolo Guglielmi (P)

a Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome , Rome , Italy.

Simone Carradori (S)

b Department of Pharmacy, "G. D'Annunzio", University of Chieti-Pescara , Chieti , Italy.

Daniela Secci (D)

a Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome , Rome , Italy.

Celeste De Monte (C)

a Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome , Rome , Italy.

Barbara De Filippis (B)

b Department of Pharmacy, "G. D'Annunzio", University of Chieti-Pescara , Chieti , Italy.

Cristina Maccallini (C)

b Department of Pharmacy, "G. D'Annunzio", University of Chieti-Pescara , Chieti , Italy.

Rosa Amoroso (R)

b Department of Pharmacy, "G. D'Annunzio", University of Chieti-Pescara , Chieti , Italy.

Roberto Cirilli (R)

c Centro Nazionale per il Controllo e la Valutazione dei Farmaci, Istituto Superiore di Sanità , Rome , Italy.

Atilla Akdemir (A)

d Computer-aided Drug Discovery Laboratory, Faculty of Pharmacy, Department of Pharmacology, Bezmialem Vakif University , Fatih, Istanbul , Turkey.

Andrea Angeli (A)

e Neurofarba Department, Section of Pharmaceutical and Nutraceutical Sciences, Università degli Studi di Firenze , Sesto Fiorentino (Florence) , Italy.

Claudiu T Supuran (CT)

e Neurofarba Department, Section of Pharmaceutical and Nutraceutical Sciences, Università degli Studi di Firenze , Sesto Fiorentino (Florence) , Italy.

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Classifications MeSH