Abstract
Purpose: To evaluate the activities of new curcumin analogs as carbonic anhydrase II (CA-II) inhibitor. Methods: Carbonic anhydrase II (CA-II) inhibition was determined by each ligand capability to inhibit the esterase activity of CA-II using 4-NPA as a substrate in 96-well plates. Dimethyl sulfoxide was used to dissolve each curcumin analog compound, and then diluted with biological buffer. They were then mixed with CA-II solution and to start the reaction, 4-NPA was added. Hydrolysis of the substrate was evaluated at 405 nm after incubation for 2 h at 25 °C. The IC 50 value of compounds with inhibitory activity higher than 40 % was then evaluated. Molecular docking was also used to predict enzymeinhibitor interaction. Results: Eight new curcumin analogs were potent to inhibit CA-II activity with IC 50 values ranging from 7.92 ± 0.54 to 72.31 ± 2.21 μmol; the lowest value was exhibited by (3E,5E)-3,5-bis[(2- hydroxyphenyl)methylidene]piperidin-4-one (a1). Molecular docking analysis revealed that this molecule formed hydrogen bonds with Thr199, Thr200 and Gln92 at the active site of CA-II. Conclusion: These curcumin analogs have inhibitory potential against CA-II; (3E, 5E)-3,5-bis[(2- hydroxyphenyl)methylidene]piperidin-4-one (a1) has the highest inhibitory activity and may be useful in the development of CA-II inhibitors for glaucoma treatment. Keywords: Carbonic anhydrase II inhibitor, Curcumin analogs, Molecular docking
Highlights
The general function of carbonic anhydrase (CA) is to catalyze the reversible conversion of carbon dioxide and water to a bicarbonate ion and a proton [1,2,3]
In order to evaluate the potential of the 44 curcumin analogs listed in Table 1 to inhibit carbonic anhydrase II (CA-II) activity, we first measured the CA-II activity in the absence and presence of each analog
The level of inhibition was expressed as the percentage difference in CA-II activity before and after the addition of the inhibitor (Table 2)
Summary
The general function of carbonic anhydrase (CA) is to catalyze the reversible conversion of carbon dioxide and water to a bicarbonate ion and a proton [1,2,3]. Sulfonamide compounds, which are known as strong inhibitors of CA-II, have been used as commercial drugs to treat glaucoma [6] These drugs produce many undesired side effects. The assay was divided into two sections—a pretest and an evaluation test The former was performed to screen inhibitor molecules that have at least a 40 % inhibitory effect, while the latter was undertaken by measuring IC50 values for the molecules selected in the previous test. Inhibitory activity was expressed as IC50 values (the concentration at which 50 % of the enzyme activity inhibited), which were calculated using Microsoft Excel 2011 from a dose-response curve obtained using at least five concentrations (ranging from 1–10 μg/mL) of the inhibitor and carried out in triplicate. Statistical analysis was performed by t-test using Microsoft Excel 2011, and p < 0.05 was considered statistically significant
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