N-methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)piperidin-4-yl)propoxy)-1H-indol-2-yl)methyl)prop-2-yn-1-amine, a new cholinesterase and monoamine oxidase dual inhibitor

On the basis of N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)-N-methylprop-2-yn-1-amine (II, ASS234) and QSAR predictions, in this work we have designed, synthesized, and evaluated a number of new indole derivatives from which we have identified N-methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)piperidin-4-yl)propoxy)-1H-indol-2-yl)methyl)prop-2-yn-1-amine (2, MBA236) as a new cholinesterase and monoamine oxidase dual inhibitor.PostprintPostprintPeer reviewe

Constrained variable clustering and the best basis problem in functional data analysis

International audienceFunctional data analysis involves data described by regular functions rather than by a finite number of real valued variables. While some robust data analysis methods can be applied directly to the very high dimensional vectors obtained from a fine grid sampling of functional data, all methods benefit from a prior simplification of the functions that reduces the redundancy induced by the regularity. In this paper we propose to use a clustering approach that targets variables rather than individual to design a piecewise constant representation of a set of functions. The contiguity constraint induced by the functional nature of the variables allows a polynomial complexity algorithm to give the optimal solution

The genetics of POAG in black South Africans: A candidate gene association study

10.1038/srep08378Scientific Reports5837

Exploring the structural basis of the selective inhibition of monoamine oxidase A by dicarbonitrile aminoheterocycles:Role of Asn181 and Ile335 validated by spectroscopic and computational studies

Since cyanide potentiates the inhibitory activity of several monoamine oxidase (MAO) inhibitors, a series of carbonitrile-containing aminoheterocycles was examined to explore the role of nitriles in determining the inhibitory activity against MAO. Dicarbonitrile aminofurans were found to be potent, selective inhibitors against MAO A. The origin of the MAO A selectivity was identified by combining spectroscopic and computational methods. Spectroscopic changes induced in MAO A by mono- and dicarbonitrile inhibitors were different, providing experimental evidence for distinct binding modes to the enzyme. Similar differences were also found between the binding of dicarbonitrile compounds to MAO A and to MAO B. Stabilization of the flavin anionic semiquinone by monocarbonitrile compounds, but destabilization by dicarbonitriles, provided further support to the distinct binding modes of these compounds and their interaction with the flavin ring. Molecular modeling studies supported the role played by the nitrile and amino groups in anchoring the inhibitor to the binding cavity. In particular, the results highlight the role of Asn181 and Ile335 in assisting the interaction of the nitrile-containing aminofuran ring. The network of interactions afforded by the specific attachment of these functional groups provides useful guidelines for the design of selective, reversible MAO A inhibitors