Affiliation:
1. Faculty of Chemistry VNU University of Science 19 Le Thanh Tong, Hoan Kiem Ha Noi 100992 Viet Nam
2. Institute of Science and Technology Ministry of Public Security of Vietnam 47 Pham Van Dong, Cau Giay Ha Noi 122300 Viet Nam
3. Institute of New Technology, Academy of Military Science and Technology Ministry of Defence 17 Hoang Sam, Cau Giay Ha Noi 122300 Viet Nam
4. Faculty of Chemical Technology Viet Tri University of Industry Tien Kien, Lam Thao Phu Tho 35259 Viet Nam
Abstract
AbstractA series of different isatin‐thiosemicarbazones 4 a–4 t derived from corresponding substituted isatins and N‐(2,3,4,6‐tetra‐O‐acetyl‐β‐d‐galactopyranosyl)thiosemicarbazide had been synthesized. Their anti‐Alzheimer activity were studied through the inhibitions of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Most of these compounds exhibited inhibitory activities against these enzymes. Of these isatin N‐(2,3,4,6‐tetra‐O‐acetyl‐β‐d‐galactoranosyl)thiosemicarbazones 4 a–4 t, in IC50 range below 0.05 μM, some thiosemicarbazones exhibited potent inhibitory activity against AChE enzyme, including 4 s (1‐benzyl)>4 t (1‐phenthyl)>4 p (1‐allyl)>4 r (1‐t‐butyl), and others exhibited potent inhibitory activity against BChE, including 4 t (1‐phenthyl)>4 o (1‐propyl)>4 q (1‐butyl)> 4 s (1‐benzyl). Enzymic kinetics of AChE and BChE inhibition of 4 s and 4 t, were studied. These compounds with strong inhibitory activity had been further investigated in induced fit docking studies as well as molecular dynamics simulations. The obtained resulting simulations indicate that strong ligand‐residues interactions were decisive factors to inhibitory activity of 4 s and 4 t against AChE and BChE enzymes, respectively.