Neuroprotective effects of a brain permeant 6-aminoquinoxaline derivative in cell culture conditions that model the loss of dopaminergic neurons in Parkinson disease

New 6-Aminoquinoxaline Derivatives with Neuroprotective Effect on Dopaminergic Neurons in Cellular and Animal Parkinson Disease Models

“…Interestingly, this compound also exerted antioxidant effects. 12 In order to improve the neuroprotective activity of compound 5c, we designed and synthesized derivatives and carried out their screening using the same PD cellular model as before. 12 For that, several structural modifications were designed based on our previous studies, which reported that the phenyl ring in position 3 of the quinoxaline core structure is important for neuroprotection.…”

“…12 In order to improve the neuroprotective activity of compound 5c, we designed and synthesized derivatives and carried out their screening using the same PD cellular model as before. 12 For that, several structural modifications were designed based on our previous studies, which reported that the phenyl ring in position 3 of the quinoxaline core structure is important for neuroprotection. 12 In addition, the presence of a C16 aliphatic chain on an Nalkyl-6-aminoquinoxaline derivative was correlated with a neuritogenic activity.…”

“…Note that 5c is inactive at 50 µM. 12 DbcAMP (1 mM) is used as reference protective molecule for DA neurons. Inactive 6-aminoquinoxaline derivatives (4s, 4t, 5b, 5d, 5f, 5g, 5h, 5i, 5k, 6d, 9c) are not included in the figure.…”

“…25,26,27 In particular, we have shown that the reference compound dbcAMP and 5c were protective by decreasing glial cell proliferation. 12,28 Therefore, we wished to have first a rough estimate of the impact that 6-aminoquinoxaline derivatives may have on glial cells. For that, we determined semi-quantitatively whether test compounds had an effect on the density and morphology of glial cells that were labelled with the glial marker protein, vimentin, using fluorescence microscopic examination of the cultures.…”

Identification of a Novel 1,4,8-Triazaphenanthrene Derivative as a Neuroprotectant for Dopamine Neurons Vulnerable in Parkinson’s Disease

“…19,20 For instance, we have shown that the reference neuroprotectant dbcAMP and also one of the previous hit compounds MPAQ were protective via a mechanism of this kind. 13,20 For that reason, we wished to determine whether 5m had a similar effect. Thus, we used a DNA proliferation assay that consists in measuring the incorporation of thymidine, [methyl-3 H], a tritiated analog of the nucleoside thymidine.…”