Schiff bases and their amines: Synthesis and discovery of carbonic anhydrase and acetylcholinesterase enzymes inhibitors

Abstract

Three series of symmetrical Schiff bases were synthesized from 1,2-diaminoethane, 1,3-diaminopropane and 1,4-diaminobutane and substituted benzaldehydes, and reduced by sodium borohydride to the corresponding benzylic diamines 4-6. All of the compounds obtained were characterized using elemental analysis, FT-IR, H-1 NMR, and C-13 NMR spectroscopy. The enzyme inhibitory properties of these compounds were tested and the influence of the alkane chain length and the substituents on the phenyl group on the enzyme inhibition activity were examined. The novel Schiff bases and their amine derivatives (1a-d, 2a-d, 3b-d, 4a-c, 5a-c, 6a, 6c, 6d) were effective inhibitors of the cytosolic carbonic anhydrase I and II isoforms (hCA I and II), and acetylcholinesterase (AChE) with K-i values in the range of 159.43 +/- 30.03 to 563.73 +/- 115.30nM for hCA I, 104.88 +/- 18.44 to 524.32 +/- 95.03nM for hCA II, and 3.95 +/- 0.74 to 30.83 +/- 6.81nM for AChE.