Benoit Daoust

Brassinosteroids and analogs as neuroprotectors: Synthesis and structure–activity relationships

We have demonstrated previously that the brassinosteroid (BR) 24-epibrassinolide exerts neuroprotective effects deriving from its antioxidative properties. In this study, we synthesized 2 natural BRs and 5 synthetic analogs and analyzed their neuroprotective actions in neuronal PC12 cells, against 1-methyl-4-phenylpyridinium (MPP(+)), a neurotoxin known to induce oxidative stress and degenerescence of dopaminergic neurons characteristic of Parkinsonian brains. We also tested the neuroprotective potential of 2 commercially available BRs. Our results disclosed that 6 of the 9 BRs and analogs tested protected neuronal PC12 cells against MPP(+) toxicity. In addition, our structure-activity study suggests that the steroid B-ring and lateral chain play an important role for their neuroprotective action.

Dopamine D2 agonists, bromocriptine and quinpirole, increase MPP+-induced toxicity in PC12 cells

Dopaminergic cell loss in the mesencephalic substantia nigra is the hallmark of Parkinson’s disease and may be associated with abnormal oxidative metabolic activity. However, the delicate balance underlying dopamine decline and oxidative stress is still a matter of debate. The aim of this study was to analyze the possible modulation of dopamine D2 agonists and antagonists on MPP+ (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium ion) -induced cellular death in differentiated and undifferentiated PC12 cells. Using colorimetric assays, western blots and reverse transcriptase-PCR, we demonstrated that two D2 agonists, bromocriptine and quinpirole, consistently increased MPP+-induced cytotoxicity in both differentiated and undifferentiated PC12 cells, whereas D2 antagonists did not modulate cell death. However, this increase in cellular death was reversed when bromocriptine or quinpirole were used in the presence of D2 antagonists. On the other hand, 1-2-[bis-(4-fluorophenyl)methoxy]ethyl-4-(3-phenylpropyl)piperazine (GBR 12909) a potent inhibitor of the dopamine transporter, partially reversed MPP+-induced cellular death and completely abolished the increase of cellular death induced by bromocriptine. Dopamine agonists and antagonists also modulate the expression of the dopamine transporter in PC12 cells; in particular, bromocriptine may alter MPP+ uptake by increasing DAT expression. We also show that, in our cellular paradigm, D2 receptor mRNA levels are more abundant that D3 mRNA levels and MPP+ and/or bromocriptine could not modulate D2 gene expression while D3 gene expression clearly decreased after MPP+ and/or bromocriptine treatment.

Synthesis of γ,δ-Unsaturated α-Aminoaldehydes Using a Copper-Catalyzed Vinylation Reaction Followed by a Claisen Rearrangement

A new method to synthesize γ,δ-unsaturated α-nitrogenated aldehydes in very good yields is described herein. This method involves a copper-coupling reaction between β-iodoenamide derivatives and allylic alcohols to generate β-allyloxyenamide derivatives. The latter, when heated, undergo a Claisen rearrangement and form γ,δ-unsaturated α-nitrogenated aldehydes.

Comparison of various alkyl cyanoacrylates for fingerprint development

ABSTRACT The ability of cyanoacrylates (CA) to develop fingerprints was first discovered in 1977. Since then, the cyanoacrylate fuming method has reached widespread use, becoming one of the primary techniques for processing fingerprints. It has, however, almost exclusively been limited to the use of ethyl cyanoacrylate, even though many other alkyl CAs could theoretically be used for this purpose, potentially with a higher efficacy. In order to examine the possibility, cyanoacrylate fuming methods for the processing of fingerprints were optimized for four different CAs: methyl, ethyl, n-butyl and 2-octyl. The development quality and sensitivity yielded by these CAs were then compared using depletion series of natural fingerprints deposited by six donors on three types of surfaces (glass, metal and plastic) and aged during three different periods of time (less than 24h, one week and one month). It was found that, on most age/surface pairs tested, butyl CA produced equivalent or even better results than ethyl CA. Scanning electron microscopy showed that ethyl and butyl CAs generally formed polymer microstructures that scatter light more effectively than methyl and octyl CAs, hence allowing higher visibility of prints processed with these cyanoacrylates.

Structural Characterization of a Novel Antioxidant Pigment Produced by a Photochromogenic Microbacterium oxydans Strain

The Microbacteriaceae family, such as Microbacterium, is well known for its ability to produce carotenoid-type pigments, but little has been published on the structure of such pigments. Here, we isolated the yellow pigment that is responsible for the yellowish color of a Microbacterium oxydans strain isolated from a decomposing stump of a resinous tree. The pigment, which is synthesized when the bacterium is grown under light, was purified and characterized using several spectroscopic analyses, such as ultraviolet-visible spectroscopy (UV–Vis), Fourier transform infrared spectroscopy (FTIR), 1H and 13C nuclear magnetic resonance (1H NMR, 13C NMR), and high-resolution mass spectrometry (HRMS). From these analysis, a molecular formula (C27H42O2) and a chemical structure (8-hydroxymethyl-2,4,12-trimethyl-14-(2,6,6-trimethyl-cyclohex-2-enyl)-teradeca-3,7,9,11,13-pentan-2-ol) were deduced. The chemical properties of the pigment, such as aqueous stability at different pH, stability in different organic solvents, and antioxidant capacity, are also reported. Together, these data and previous studies have resulted in the identification of a new antioxidant pigment produced by M. oxydans. To the best of our knowledge, this is the first thorough investigation of this carotenoid-like pigment in the Microbacterium genera.