Synthesis and characterization of phenolic Mannich bases and effects of these compounds on human carbonic anhydrase isozymes I and II

Abstract

Mannich bases 2a-f derived from 3,4-dimethylphenol (1), formaldehyde and different amines are prepared and subjected to spectral (IR, ¹H and ¹³C NMR) and elemental analyses. The inhibition of two human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II, with 1 and synthesized Mannich bases 2a-f and acetazolamide (AAZ) as a control compound was investigated in vitro by using the hydratase and esterase assays. In relation to hydratase and esterase activities of the half maximal inhibitory concentration (IC₅₀) and the inhibition equilibrium constants (K_i)values were determined. Only two compounds (2a and 2e)exhibit weak hCA II inhibitory effects on esterase activity. IC₅₀ and Ki values for 2a and 2e with respect to esterase activity of hCA II are0.88 × 10³ and 6.3–7.6 µM and 0.44 × 10³ and 19.0–96.4 µM,respectively. On the contrary, compounds 2b and 2d might be used as CA activators due to increasing esterase activity of hCA I and hCA II isozymes.

Keywords::

• Mannich base
• 3,4-dimethylphenol
• NMR
• carbonic anhydrase
• hydratase and esterase activities