In Vitro Inhibition of Human Carbonic Anhydrase I and II Isozymes with Natural Phenolic Compounds

Abstract

Inhibition of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II with some natural phenolic derivatives was investigated using the esterase assay with 4-nitrophenyl acetate as substrate. Resveratrol, catechin, silymarin, dobutamin, and curcumin showed K(I) values in the range of 4.47-9.47 mm for hCA I and of 2.86-7.44 μm against hCA II, respectively. These natural product phenols were generally competitive inhibitors with 4-nitrophenylacetate as substrate. Some natural phenols investigated here showed effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide acetazolamide, and might be used as leads for generating enzyme inhibitors possibly targeting other CA isoforms that have not been yet assayed for their interactions with such agents.

Determination of activities of human carbonic anhydrase II inhibitors from curcumin analogs

“…Previously, curcumin has been shown to inhibit CA-II [9]. In this study, eight new curcumin analogs also showed to effectively inhibit CA-II at the micromolar range.…”

“…Curcumin and related compounds show promising result as a molecular base on which to design novel inhibitors of CA-II [9]. Due to the amounts and the variety of curcuminoids from natural sources are limited, methods of synthesizing curcumin and its analogs have been explored [10].…”

Synthesis of N-alkyl (aril)-tetra pyrimidine thiones and investigation of their human carbonic anhydrase I and II inhibitory effects

“…However, it is found in rodents and other higher vertebrates. Three acatalytic forms are known and called CArelated proteins (CARP) [49][50][51] . The dimeric transmembrane glycoproteins hCA IX and XII are also isoforms having an extracellular active site and are markers for a broad spectrum of hypoxic tumors [52][53][54] .…”

“…A single band was observed for each hCA isoenzyme. Both CA isoenzymes activities were determined in accordance with the method of Verpoorte et al 77 described previously 47,49 . The increasing absorbance at 348 nm of p-nitrophenylacetate (NPA) to p-nitrophenolate (NP) was recorded during a short period (3 minutes) at 25 C using a spectrophotometer (Shimadzu, UV-VIS Spectrophotometer, UVmini-1240).…”

Synthesis and inhibitory properties of some carbamates on carbonic anhydrase and acetylcholine esterase

“…In humans, CAs are dispersed in different tissues including the reproductive tract, the gastrointestinal tract, kidneys, the nervous system, skin, eyes, lungs, and among some others [35][36][37][38] . Carbonic anhydrase isoenzymes contain a zinc ion (Zn 2+ ) in their active site, coordinated by three His residues and a H 2 O molecule/hydroxide ion (ÀOH) in the a-and g-CAs or by two Cys and one His residues (in the b class), with the fourth ligand being a H 2 O molecule/ÀOH ion acting as nucleophile in the catalyzed reactions [39][40][41][42][43] . Cytosolic hCA I and II isoforms are spread throughout the human body and are drug targets for clinically used antiglaucoma, anticonvulsants and diuretics drugs [44][45][46][47] .…”