Analysis of the antioxidant properties of differently substituted 2- and 3-indolyl carbohydrazides and related derivatives

• 2- and 3-indolyl carbohydrazides and hydrazine derivatives as anti-Alzheimer drugs.
• Antioxidant properties of carbohydrazides.
• Hydrazides JL40 and JL432 showed higher lipoxygenase inhibitory activity.
• Compounds JL40 and JL432 presented promising anti-inflammatory in vivo results.

Herein, we report the antioxidant properties of some selected substituted 2-indolyl carbohydrazides (JL34, JL40, JL71, JL87, JL317, JL432, JL436), the substituted 3-indolyl carbohydrazide JL344, 3-(3-hydrazinylpropyl)-1H-indole (JL72) and 3-(1H-indol-3-yl)propanehydrazide (JL418), throughout the assessment of their antioxidative potential using different antioxidant assays such as DPPH, lipid peroxidation in the APPH, or the DMSO method. We conclude that these compounds are convenient templates for the design of useful drugs in to treat Alzheimer's disease (AD), a pathology characterized by extensive oxidative stress and inflammation, thus essentially affected by reactive oxygen species (ROS). Most of them are potent hydroxyl radical scavengers and inhibit in vitro lipid peroxidation. Compounds JL40 and JL432 presenting higher lipoxygenase inhibitory activity among the tested derivatives, were found to present a promising anti-inflammatory in vivo result, as well as antioxidant and LOX inhibitory profile. These results in combination to their known AChE/BuChE inhibitory activities led us to propose these indolyl carbohydrazides as new multifunctional compounds against AD.

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