Title:Quinolinic Carboxylic Acid Derivatives as Potential Multi-target Compounds for Neurodegeneration: Monoamine Oxidase and Cholinesterase Inhibition
VOLUME: 14 ISSUE: 1
Author(s):Nehal A. Khan, Imtiaz Khan, Syed M.A. Abid, Sumera Zaib, Aliya Ibrar, Hina Andleeb, Shahid Hameed* and Jamshed Iqbal*
Affiliation:Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad-22060, Department of Chemistry, Quaid-i-Azam University, Islamabad-45320, Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad-22060, Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad-22060, Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad-22060, Department of Chemistry, Quaid-i-Azam University, Islamabad-45320, Department of Chemistry, Quaid-i-Azam University, Islamabad-45320, Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad-22060
Keywords:Cholinesterase inhibition, drug-likeness, molecular docking, monoamine oxidases, parkinson's disease, quinoline
carboxylic acids.
Abstract:Background: Parkinson's disease (PD), a debilitating and progressive disorder, is among
the most challenging and devastating neurodegenerative diseases predominantly affecting the people
over 60 years of age.
Objectives: To confront PD, an advanced and operational strategy is to design single chemical
functionality able to control more than one target instantaneously.
Methods: In this endeavor, for the exploration of new and efficient inhibitors of Parkinson's disease,
we synthesized a series of quinoline carboxylic acids (3a-j) and evaluated their in vitro monoamine
oxidase and cholinesterase inhibitory activities. The molecular docking and in silico studies of the
most potent inhibitors were performed to identify the probable binding modes in the active site of the
monoamine oxidase enzymes. Moreover, molecular properties were calculated to evaluate the druglikeness
of the compounds.
Results: The biological evaluation results revealed that the tested compounds were highly potent
against monoamine oxidase (A & B), 3c targeted both the isoforms of MAO with IC50 values of 0.51
± 0.12 and 0.51 ± 0.03 µM, respectively. The tested compounds also demonstrated high and completely
selective inhibitory action against acetylcholinesterase (AChE) with IC50 values ranging from
4.36 to 89.24 µM. Among the examined derivatives, 3i was recognized as the most potent inhibitor
of AChE with an IC50 value of 4.36 ± 0.12 ±µM.
Conclusion: The compounds appear to be promising inhibitors and could be used for the future development
of drugs targeting neurodegenerative disorders.
