Investigations on the 2-thiazolylhydrazyne scaffold: synthesis and molecular modeling of selective human monoamine oxidase inhibitors.

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Chimenti F, Bolasco A, Secci D, Chimenti P, Granese A, Carradori S, Yanez M, Orallo F, Ortuso F, Alcaro S

Investigations on the 2-thiazolylhydrazyne scaffold: synthesis and molecular modeling of selective human monoamine oxidase inhibitors.

Bioorg Med Chem. 2010 Aug 1;18(15):5715-23. doi: 10.1016/j.bmc.2010.06.007. Epub 2010 Jun 9.

PubMed ID
20615716 [ View in PubMed
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Abstract

A new series of [4-(3-methoxyphenyl)-thiazol-2-yl]hydrazyne derivatives were synthesized in good yield (71-99%) and characterized by elemental analysis and (1)H NMR studies. The compounds were assayed for their in vitro human monoamine oxidase (hMAO) inhibitory activity and selectivity and most of them showed IC(50) values in the nanomolar range, thus demonstrating our interest in this privileged scaffold. The most active and selective derivative (20), bearing a pyridine moiety on the CN, displayed IC(50)=3.81+/-0.12 nM and selectivity ratio=119 toward hMAO-B. Molecular modeling studies were carried out on recent and high resolution hMAO-A and hMAO-B crystallographic structures to better justify the enzyme-inhibitor interaction toward hMAO isoforms and to explain the structure-activity relationship of this kind of inhibitors.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
ClorgilineAmine oxidase [flavin-containing] AIC 50 (nM)4.46N/AN/ADetails
IproniazidAmine oxidase [flavin-containing] BIC 50 (nM)7540N/AN/ADetails
IsatinAmine oxidase [flavin-containing] BIC 50 (nM)18750N/AN/ADetails
MoclobemideAmine oxidase [flavin-containing] AIC 50 (nM)361380N/AN/ADetails
SelegilineAmine oxidase [flavin-containing] AIC 50 (nM)67250N/AN/ADetails
SelegilineAmine oxidase [flavin-containing] BIC 50 (nM)19600N/AN/ADetails