RESUMO
Two closely related hybrid species containing both, thiazolyl and coumarin groups, were synthesized by using two different one-pot procedures from a common precursor. The reaction of α-bromoacetylcoumarin with thioacetamide in methanol furnished 3(2methylthiazol4yl)2Hchromen2one (2), whereas refluxing αbromoacetylcoumarin with potassium thiocyanate in ethanol afforded 3(2ethoxythiazol4yl)2Hchromen2one (3). Both derivatives were fully characterized by spectroscopic methods, elemental analysis and X-ray diffraction studies. Intramolecular C4Hâ¯N and C5'Hâ¯OC hydrogen bonds between the heterocycles determine the conformational behavior. The co-planarity of the coumarin and thiazolyl rings favors the occurrence of two remote orbital interactions involving the oxygen and nitrogen lone pairs and the corresponding σ*CH electron acceptor, as demonstrated by Natural Bond Orbital population analysis. The 2-substitution of the thiazol4yl group has little effect on the molecular structures but causes significant differences in the crystal packing of the two compounds.
RESUMO
On the basis of the observed biological activity of the coumarins, a new set of 3-thiazolocoumarinyl Schiff-base derivatives with chlorine, hydroxy and methoxy functional group substitutions were designed and synthesized. These compounds were tested against acetylcholinesterase from Electrophorus electricus and butyrylcholinesterase from horse serum and their structure-activity relationship was established. Studies revealed them as the potential inhibitors of cholinesterase (acetylcholinesterase and butyrylcholinesterase). The 3f was found to be most potent against acetylcholinesterase with K(i) value of 1.05 ± 0.3 µM and 3l showed excellent inhibitory action against butyrylcholinesterase with K(i) value of 0.041 ± 0.002 µM. The synthesized compounds were also docked into the active sites of the homology models of acetylcholinesterase and butyrylcholinesterase to predict the binding modes of these compounds. It was predicted that most of the compounds have similar binding modes with reasonable binding affinities. Our docking studies have also shown that these synthesized compounds have better interaction patterns with butyrylcholinesterase over acetylcholinesterase. The main objective of the study was to develop new potent and selective compounds, which might be further optimized to prevent the progression of the Alzheimer's disease and could provide symptomatic treatment.