Synthesis, characterization, crystal structures, theoretical calculations and biological evaluations of novel substituted tacrine derivatives as cholinesterase and carbonic anhydrase enzymes inhibitors

Abstract

The six and seven hydrocycle membered disilylanilino acridine (tacrine) analogues (9–11) were synthesized by one-pot procedures. The structures of novel silyl tacrine derivatives were characterized by NMR spectroscopy, elemental analysis and XRD investigations. The silyl substituted novel tacrine derivatives (9–11) were investigated as cholinesterase inhibitors and defined the relative role of AChE (Acetylcholinesterase) versus BChE (Butyrylcholinesterase) inhibition. Novel substituted tacrine derivatives are known as important inhibitors of Carbonic anhydrase (CA) isoenzymes I, and II (hCA I and II), therefore, the synthesized compounds (9–11) were investigated for inhibitory effects on the both CA isoenzymes. Additionally, we evaluated four different enzymes, which were inhibited in the very low nanomolar (nM) range by these compounds. According to the present studies, for AChE, BChE, hCA I and II, the ranges of results are recorded as 30.26 ± 6.71–117.54 ± 42.22 nM, 22.45 ± 5.81–77.41 ± 4.02 nM, 57.28 ± 22.16–213.41 ± 82.75 nM and 46.95 ± 11.32–274.94 ± 62.15 nM, respectively.