Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Reza Aditama¹, Yum Eryanti², Didin Mujahidin³, Yana Maolana Syah³, Rukman Hertadi¹

¹Biochemistry Research Group, Faculty of Mathematics and Natural Sciences, Bandung Institute of Technology, Jalan Ganesha 10, Bandung 40132; ²Laboratory of Organic Synthesis, Department of Chemistry, Faculty of Mathematics and Natural Sciences, University of Riau, Pekanbaru, 26293; ³Organic Research Group, Faculty of Mathematics and Natural Sciences, Bandung Institute of Technology, Jalan Ganesha 10, Bandung 40132, Indonesia.

For correspondence:- Rukman Hertadi Email: rukman@chem.itb.ac.id Tel:+6281321174370

Received: 2 November 2016 Accepted: 9 March 2017 Published: 30 April 2017

Citation: Aditama R, Eryanti Y, Mujahidin D, Syah YM, Hertadi R. Determination of activities of human carbonic anhydrase II inhibitors from curcumin analogs. Trop J Pharm Res 2017; 16(4):849-854 doi: 10.4314/tjpr.v16i4.14

© 2017 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

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 IC₅₀ value of compounds with inhibitory activity higher than 40 % was then evaluated. Molecular docking was also used to predict enzyme-inhibitor interaction.

Results: Eight new curcumin analogs were potent to inhibit CA-II activity with IC₅₀ 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