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Bioorg Med Chem. 2015 Nov 15;23(22):7219-25. doi: 10.1016/j.bmc.2015.10.018. Epub 2015 Oct 20.

New natural product carbonic anhydrase inhibitors incorporating phenol moieties.

Author information

1
Laboratory of Pharmacognosy, School of Pharmacy, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
2
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
3
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy. Electronic address: fabrizio.carta@unifi.it.
4
Università degli Studi di Firenze, PHYTOLAB, Departimento di Chimica Ugo Schiff, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy.
5
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy; Università degli Studi di Firenze, Polo Scientifico, Dipartimento NEUROFARBA, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy. Electronic address: claudiu.supuran@unifi.it.

Abstract

Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. They represent a typical example of enzyme convergent evolution, as six genetically unrelated families of such enzymes were described so far. The need to find selective CA inhibitors (CAIs) triggered the investigation of natural product libraries, which proved to be a valid source of agents with such an activity, as demonstrated for the phenols, polyamines and coumarins. Herein we report an in vitro inhibition study of human (h) CA isoforms hCAs I, II, IV, VII and XII with a panel of natural polyphenols including flavones, flavonols, flavanones, flavanols, isoflavones and depsides, some of which extracted from Quercus ilex and Salvia miltiorrhiza. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting some important isoforms over the off-target ones hCA I and II.

KEYWORDS:

Carbonic anhydrase inhibitors (CAIs); Metalloenzymes; Natural products; Phenol; Polyphenols

PMID:
26498393
DOI:
10.1016/j.bmc.2015.10.018
[Indexed for MEDLINE]

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