Synthesis and carbonic anhydrase inhibitory properties of novel bromophenols including natural products

Abstract

(2-Bromo-3,4-dimethoxyphenyl) (3,4-dimethoxyphenyl)methanone (10) and its derivatives with Br, one dibromide and isomeric three tribromides, were synthesized. Demethylation of these compounds afforded a series of new bromophenols. Inhibition of human cytosolic carbonic anhydrase II (hCA II) isozyme by these new bromophenols and naturally occurring 3,4,6-tribromo-5-(2,5-dibromo-3,4-dihydroxybenzyl)benzene-1,2-diol (3), and 5,5′-methylenebis(3,4,6-tribromo-benzene-1,2-diol) (4) was investigated. The synthesized compounds showed carbonic anhydrase inhibitory capacities with IC₅₀ values in the range of 0.7–372 μM against hCA II. Some bromophenols investigated here showed effective hCA II inhibitory activity and might be used as leads for generating novel carbonic anhydrase inhibitors which are valuable drug candidates for the treatment of glaucoma, epilepsy, gastric and duodenal ulcers, neurological disorders, or osteoporosis.

Keywords::

• Bromophenols
• diphenylmethane
• carbonic anhydrase
• glaucoma
• enzyme inhibition

Acknowledgment

The authors are indebted to the Department of Chemistry (Atatürk University) for research conditions.

Declaration of interest

This research was financed by grants from of TÜBİTAK (The Scientific and Technological Research Council of Turkey) (Project no: TBAG-107T348).