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

Autor: Giuseppe Felice Mangiatordi, Bijo Mathew, Hoon Kim, Jae Pil Lee, Seung Cheol Baek, Orazio Nicolotti, Thillainayagam Subburaju, B. Lakshminarayanan, N. Kannappan
Rok vydání: 2019
Předmět:
Zdroj: ChemistrySelect 4 (2019): 6614–6619. doi:10.1002/slct.201901093
info:cnr-pdr/source/autori:Lakshminarayanan, Balasubramanian; Baek, Seung Cheol; Lee, Jae Pil; Kannappan, Nagappan; Mangiatordi, Giuseppe Felice; Nicolotti, Orazio; Subburaju, Thillainayagam; Kim, Hoon; Mathew, Bijo/titolo:Ethoxylated Head of Chalcones as a New Class of Multi-Targeted MAO Inhibitors/doi:10.1002%2Fslct.201901093/rivista:ChemistrySelect/anno:2019/pagina_da:6614/pagina_a:6619/intervallo_pagine:6614–6619/volume:4
ISSN: 2365-6549
DOI: 10.1002/slct.201901093
Popis: 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 mu M 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 K-i values of 2.65 +/- 0.064 and 0.011 +/- 0.0011 mu M, 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 mu M, 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
Databáze: OpenAIRE
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