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Publication Type : Journal Article
Publisher : Molecules
Source : Molecules, Volume 26, Issue 11 (2021)
Keywords : blood-brain barrier, Catalytic Domain, Chemistry, Pharmaceutical, cognition, drug design, Halogens, Humans, Inhibitory Concentration 50, kinetics, Models, Chemical, Molecular Docking Simulation, Molecular Dynamics Simulation, Molecular Structure, Monoamine oxidase, Monoamine Oxidase Inhibitors, Motion, Principal component analysis, Protein Binding, Pyrazoles, Recombinant Proteins, Stereoisomerism, Structure-Activity Relationship
Campus : Kochi
School : School of Pharmacy
Department : Pharmaceutical Chemistry & Analysis
Year : 2021
Abstract : Halogens have been reported to play a major role in the inhibition of monoamine oxidase (MAO), relating to diverse cognitive functions of the central nervous system. Pyrazoline/halogenated pyrazolines were investigated for their inhibitory activities against human monoamine oxidase-A and -B. Halogen substitutions on the phenyl ring located at the fifth position of pyrazoline showed potent MAO-B inhibition. Compound 3-(4-ethoxyphenyl)-5-(4-fluorophenyl)-4,5-dihydro-1-pyrazole () showed the highest potency against MAO-B with an IC value of 0.063 µM. The potencies against MAO-B were increased in the order of -F (in ) > -Cl () > -Br () > -H (). The residual activities of most compounds for MAO-A were > 50% at 10 µM, except for and (IC = 8.38 and 4.31 µM, respectively). showed the highest selectivity index (SI) value of 133.0 for MAO-B, followed by at > 55.8. was a reversible and competitive inhibitor of MAO-B in kinetic and reversibility experiments with a Ki value of 0.034 ± 0.0067 µM. The molecular dynamics study documented that had a good binding affinity and motional movement within the active site with high stability. It was observed by MM-PBSA that the chirality had little effect on the overall binding of to MAO-B. Thus, can be employed for the development of lead molecules for the treatment of various neurodegenerative disorders.
Cite this Research Publication : A. Sujathan Nair, Oh, J. - M., Koyiparambath, V. Payyalot, Sunil Kumar, Sudevan, S. Thazhathuv, Soremekun, O., Soliman, M. E., Khames, A., Abdelgawad, M. A., Pappachen, L. K., Bijo Mathew, and Kim, H., “Development of Halogenated Pyrazolines as Selective Monoamine Oxidase-B Inhibitors: Deciphering via Molecular Dynamics Approach.”, Molecules, vol. 26, no. 11, 2021.