3-Aryl-1-phenyl-1H-pyrazole derivatives as new multitarget directed ligands for the treatment of Alzheimer's disease, with acetylcholinesterase and monoamine oxidase inhibitory properties

Authors

  • Ashwani Kumar Drug Discovery and Research Laboratory, Department of Pharmaceutical Sciences,Guru Jambheshwar University of Science and Technology, Hisar -125 001, Haryana, India
  • Sandeep Jain Drug Discovery and Research Laboratory, Department of Pharmaceutical Sciences,Guru Jambheshwar University of Science and Technology, Hisar -125 001, Haryana, India
  • Milind Parle Drug Discovery and Research Laboratory, Department of Pharmaceutical Sciences,Guru Jambheshwar University of Science and Technology, Hisar -125 001, Haryana, India
  • Neelam Jain Department of Pharmaceutical Education and Research, BPSMV, Khanpur kalan, Sonepat, Haryana, India
  • Parvin Kumar Department of Chemistry, Kurukshetra University, Kurukshetra-136119, Haryana, India

Keywords:

Alzheimer's disease, 1H-pyrazole, AChE, MAO-B, molecular modeling

Abstract

A series of 3-aryl-1-phenyl-1H-pyrazole derivatives was synthesized in good yield and assayed in vitro as inhibitors of the mice acetylcholinesterase (AChE) and two goat liver monoamine oxidase (MAO) isoforms, MAO-A and MAO-B. Most of the compounds demonstrated a good AChE and selective MAO-B inhibitory activities in the nanomolar or low micromolar range. N-((3-(4-chlorophenyl)-1-phenyl-1H-pyrazole-4-yl) methylene) benzenamine (3e, pIC50 = 4.2) and N-((4-fluorophenyl)-1-phenyl-1H-pyrazole-4-yl) methylene) methanamine (3f, pIC50 = 3.47) were the most potent AChE and highly selective MAO-B inhibitors respectively. Structure activity relationships showed that chloro derivatives were more effective AChE inhibitors as compared to fluoro derivatives while reverse trend was observed in MAO-B inhibitory activity. With the aid of modeling studies, potential binding orientations as well as interactions of the compounds in the AChE and MAO-B active sites were examined.

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Published

2013-12-13

How to Cite

Kumar, A., Jain, S., Parle, M., Jain, N., & Kumar, P. (2013). 3-Aryl-1-phenyl-1H-pyrazole derivatives as new multitarget directed ligands for the treatment of Alzheimer’s disease, with acetylcholinesterase and monoamine oxidase inhibitory properties. EXCLI Journal, 12, 1030–1042. Retrieved from https://www.excli.de/index.php/excli/article/view/1216

Issue

Vol. 12 (2013)

Section

Original articles

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