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Bioorg Chem. 2015 Oct;62:22-9. doi: 10.1016/j.bioorg.2015.07.001. Epub 2015 Jul 9.

Development of fluorinated methoxylated chalcones as selective monoamine oxidase-B inhibitors: Synthesis, biochemistry and molecular docking studies.

Author information

1
Division of Drug Design and Medicinal Chemistry Research Lab, Department of Pharmaceutical Chemistry, Grace College of Pharmacy, Palakkad 678004, Kerala, India. Electronic address: bijovilaventgu@gmail.com.
2
Department of Pharmacology, Grace College of Pharmacy, Palakkad 678004, Kerala, India.
3
Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, 06100 Sıhhiye, Ankara, Turkey.
4
Department of Pharmaceutical Chemistry, Madras Medical College, Chennai 600004, India.
5
Division of Drug Design and Medicinal Chemistry Research Lab, Department of Pharmaceutical Chemistry, Grace College of Pharmacy, Palakkad 678004, Kerala, India.

Abstract

A series of methoxylated chalcones with fluoro and trifluoromethyl derivatives were synthesized and investigated for their ability to inhibit human monoamine oxidase A and B. The chemical structures of the compounds have been characterized by means of their (1)H NMR, (13)C NMR, Mass spectroscopic datas and elemental analysis. The results demonstrate that these compounds are reversible and selective MAO-B inhibitors with a competitive mode of inhibition. The most potent compound (2E)-1-(4-methoxyphenyl)-3-[4-(trifluoromethyl)phenyl] prop-2-en-1-one showed the best activity and higher selectivity towards hMAO-B with Ki and SI values of 0.22±0.01μM and 0.05 comparable to that standard drug, Selegiline Ki and SI values were found as 0.33±0.03μM and 0.04, respectively. Molecular docking studies were carried out to further explain the in vitro results of the new compounds, and to identify the hypothetical binding mode for the compounds inside the inhibitor binding cavity of hMAO-B.

KEYWORDS:

MAO-A; MAO-B; Methoxylated chalcone; Molecular docking

PMID:
26189013
DOI:
10.1016/j.bioorg.2015.07.001
[Indexed for MEDLINE]

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