Design and development of novel p-aminobenzoic acid derivatives as potential cholinesterase inhibitors for the treatment of Alzheimer's disease.

Autor: Shrivastava SK; Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, U.P., India. Electronic address: skshrivastava.phe@iitbhu.ac.in., Sinha SK; Department of Pharmaceutical Sciences, Mohanlal Sukhadia University, Udaipur 313001, Rajasthan, India., Srivastava P; Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, U.P., India., Tripathi PN; Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, U.P., India., Sharma P; Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, U.P., India., Tripathi MK; Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, U.P., India., Tripathi A; Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, U.P., India., Choubey PK; Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, U.P., India., Waiker DK; Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, U.P., India., Aggarwal LM; Department of Radiotherapy & Radiation Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP 221 005, India., Dixit M; Department of Nuclear Medicine, SGPGIMS, Raebareli Road, Lucknow 226014, UP, India., Kheruka SC; Department of Nuclear Medicine, SGPGIMS, Raebareli Road, Lucknow 226014, UP, India., Gambhir S; Department of Nuclear Medicine, SGPGIMS, Raebareli Road, Lucknow 226014, UP, India., Shankar S; Department of Genetics, Louisiana State University Health Sciences Center, 1700 Tulane Avenue, New Orleans, LA 70112, USA., Srivastava RK; Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, 1700 Tulane Avenue, New Orleans, LA 70112, USA.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2019 Feb; Vol. 82, pp. 211-223. Date of Electronic Publication: 2018 Oct 09.
DOI: 10.1016/j.bioorg.2018.10.009
Abstrakt: Based on the quantitative structure-activity relationship (QSAR), some novel p-aminobenzoic acid derivatives as promising cholinesterase enzyme inhibitors were designed, synthesized, characterized and evaluated to enhance learning and memory. The in vitro enzyme kinetic study of the synthesized compounds revealed the type of inhibition on the respective acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The in vivo studies of the synthesized compounds exhibited significant reversal of cognitive deficits in the animal models of amnesia as compared to standard drug donepezil. Further, the ex vivo studies in the specific brain regions like the hippocampus, hypothalamus, and prefrontal cortex regions also exhibited AChE inhibition comparable to standard donepezil. The in silico molecular docking and dynamics simulations studies of the most potent compound 22 revealed the consensual interactions at the active site pocket of the AChE.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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