Synthesis, characterization, molecular docking and in vitro screening of new metal complexes with coumarin Schiff base as anticholine esterase and antipancreatic cholesterol esterase agents.

In this work, Combining coumarin and thiazole with 3-tertiary butyl salicylaldehyde into in a single molecule, new Schiff base (CTS), and its metal complexes with palladium and platinum were synthesized and characterized by using well-known spectroscopic techniques such as 1H-NMR, 13C-NMR, FT-IR and LC-MS. And also, the formation of these complexes were confirmed by magnetic moment and conductivity measurements. The photophysical properties of CTS were studied and it was observed that the Schiff base has a sensitivity to CN-, F-, and AcO- anions. The quantum chemical calculations based on density functional theory (DFT) were done for explaining some experimental, structural, and spectroscopic data of the dyes. Also, to evaluate the binding interactions between the ligand (CTS) and its metal complexes and enzymes, molecular docking studies were performed and all the compounds tested to determine its inhibition potential against the cholinesterase (AChE and BChE) and pancreatic cholesterol esterase (CEase) enzymes. Both in vitro and in silico the results showed that all of the compounds could act as potent inhibitors of AChE, BChE, and CEase. The Pt (II) complex showed the most potent inhibitory property against all of the enzymes with IC50 values of 12 µM for AChE, 23 µM for BChE, and 21 µM for CEase.Communicated by Ramaswamy H. Sarma.

New aromatic/heteroaromatic propanesulfonylhydrazone compounds: synthesis, physical properties and inhibition studies against carbonic anhydrase II (CAII) enzyme.

Some new aromatic/heteroaromatic propanesulfonylhydrazone derivatives (1-8) were synthesized and characterized by elemental analyses, FT-IR, (1)H NMR, (13)C NMR, LC/MS techniques. The geometry optimizations and spectral calculations were performed by using DFT/B3LYP/6-311G(d,p) basis set in Gaussian 09 program. The inhibition activities of the synthesized compounds on carbonic anhydrase II (CAII) isoenzyme have been investigated by comparing IC50 values. Acetazolamide (5-acetamido-1,3,4-thiadiazole-2-sulfonamide) AAZ, a clinically used in CAII inhibition has also been investigated as standard inhibitor. The best aromatic/heteroaromatic propanesulfonylhydrazone inhibitors of this isoform were o-aminobenzaldehydepropanesulfonylhydrazone (1) and thiophenecarboxyaldehyde propanesulfonylhydrazone (5) having the same IC50 (0.55 mM) value. The molecular descriptors for propanesulfonylhydrazones were obtained to develop structure activity relationship (SAR) model between experimental IC50 values and the molecular descriptors calculated by PM3-based SAR models in Hyperchem 8, respectively. The obtained models confirm the good carbonic anhydrase II (CAII) inhibition activity of the propanesulfonylhydrazone derivatives. The selected descriptors are sensitive both to the imine (CH=N) and NH2 groups that are responsible from higher activities of (1) and (5) in their series.