Investigation of in vitro and in silico effects of some novel carbazole Schiff bases on human carbonic anhydrase isoforms I and II

Abstract

Carbonic anhydrases (CAs, EC4.2.1.1) are metalloenzymes that catalyse reversible hydration reaction of carbon dioxide to bicarbonate and protons. In recent years, there has been a great interest in inhibitors/activators of carbonic anhydrase isoenzymes. Therefore, we investigated the effects of four different carbazole Schiff base derivatives, which are believed to have a potential to be used as a drug, on human carbonic anhydrase (hCA) isoenzymes I and II under in vitro conditions. The IC₅₀ values of carbazole Schiff base derivatives were found to be in the range of 32.09–151.2 μM for hCA isoenzyme I and 21.82–40.54 μM for hCA isoenzyme II. Among all compounds, (E)-3-(((9-Octyl-9H-carbazole-3-yl)imino)methyl)benzene-1,2-diol (C3) had the strongest inhibitory effect on hCA isoenzyme II. It was determined that 2,3,4-trimethoxy and 4-hydroxy phenyl containing carbazole compounds have selective inhibition against hCA II isoenzyme. Docking studies were performed against hCA I and II receptors using induced-fit docking method. The compounds had affinity scores varying from −7.74 ± 0.27 to −6.27 ± 0.07 kcal/mol for hCA I and from −8.04 ± 0.17 to −7.27 ± 0.18 kcal/mol for hCA II.

Communicated by Ramaswamy H. Sarma

Keywords:

• Carbazole
• carbonic anhydrase
• docking
• esterase activity
• inhibition
• Schiff bases

Acknowledgements

This article is an extended version of a conference presentation entitled “Investigation of the inhibitory effects some Schiff bases on isozymes hCA I and hCA II purified from human erythrocytes,” and presented in “4th International BAU Drug Design Congress” (Camadan et al., 2016).

Disclosure statement

The authors declared that they have no conflict of interest.

Human and animal rights

No humans or animals were used in this study. The human blood used in the examination was the waste blood obtained from Siirt Hospital Blood Center.

Additional information

Funding

This work was supported by a grant from the Scientific Research Project of Balıkesir University of Turkey [Grant Number: BAP.2015.0001 and Grant Number: BAP.2017/181].