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Ethoxylated Head of Chalcones as a New Class of Multi-Targeted MAO Inhibitors

Publication Type : Journal Article

Publisher : ChemistrySelect

Source : ChemistrySelect, Volume 4, Number 21, p.6614-6619 (2019)

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Keywords : AChE, Chalcone, hMAOs, MM-GBSA, Multi-targeting, QM-polarized docking, Selective competitive inhibitor

Campus : Kochi

School : School of Pharmacy

Department : Pharmaceutical Chemistry & Analysis

Year : 2019

Abstract : Abstract A series of eleven ethoxysubstituted chalcones (E1-E11) were synthesized and investigated for their inhibitory potential towards human recombinant monoamine oxidase A and B (hMAO−A and hMAO−B, respectively) and acetylcholinesterase (AChE). IC50 values of 4.63 ± 0.15 and 0.053 ± 0.003 μM were obtained for MAO−A and MAO−B, respectively, by the most interesting compound (2E)-1-(4-ethoxyphenyl)-3-(4-fluorophenyl)prop-2-en-1-one (E7), and it was characterized by a high selectivity index (SI=87.4) for MAO−B. Inhibitions by E7 against MAO−A and MAO−B were recovered (75.9 and 74.5%, respectively) to near the levels of reversible references (77.1 and 77.4%, respectively). The inhibition modes of E7 for MAO−A and MAO−B were competitive with Ki values of 2.65 ± 0.064 and 0.011 ± 0.0011 μM, respectively. Compounds (2E)-1-(4-ethoxyphenyl)-3-(4-ethylphenyl) prop-2-en-1-one (E10) and (2E)-1-(4-ethoxyphenyl)-3-[4-(trifluoromethyl)phenyl]prop-2-en-1-one (E11) showed good inhibitions against AChE with IC50 values of 2.86 ± 0.041 and 3.23 ± 0.0073 μM, respectively. A combined molecular docking/MM-GBSA approach was used that employed quantum mechanics (QM) partial charges; this technique revealed the molecular rationale behind the observed MAO−B selectivity for this molecular series. Taken together, these results indicate that E7 is a potent, selective and reversible competitive inhibitor of MAO−B with moderately potent AChE inhibitory activity that has potential as a multi-targeting drug

Cite this Research Publication : B. Lakshminarayanan, Baek, S. Cheol, Lee, J. Pil, Kannappan, N., Mangiatordi, G. Felice, Nicolotti, O., Subburaju, T., Kim, H., and Bijo Mathew, “Ethoxylated Head of Chalcones as a New Class of Multi-Targeted MAO Inhibitors”, ChemistrySelect, vol. 4, pp. 6614-6619, 2019.

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