Neurotropic activity and safety of methylene-cycloalkylacetate (MCA) derivative 3‑(3-allyl-2-methylenecyclohexyl) propanoic acid

Polyneuropathy is a disease involving multiple peripheral nerves injuries. Axon regrowth remains the major prerequisite for plasticity, regeneration, circuit formation, and eventually functional recovery and therefore, regulation of neurite outgrowth might be a candidate for treating polyneuropathie...

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Published in:ACS chemical neuroscience 2020-09, Vol.11 (17), p.2577-2589
Main Authors: Lahiani, Adi, Haham-Geula, Dikla, Lankri, David, Cornell-Kennon, Susan, Schaefer, Erik M, Tsvelikhovsky, Dmitry, Lazarovici, Philip
Format: Article
Language:English
Subjects:
Animals
Axons
Cells, Cultured
Ganglia, Spinal
Mice
Nerve Regeneration
Neurites
Neuronal Outgrowth
Propionates
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Summary:Polyneuropathy is a disease involving multiple peripheral nerves injuries. Axon regrowth remains the major prerequisite for plasticity, regeneration, circuit formation, and eventually functional recovery and therefore, regulation of neurite outgrowth might be a candidate for treating polyneuropathies. In a recent study, we synthesized and established the methylene-cycloalkylacetate (MCAs) pharmacophore as a lead for the development of a neurotropic drug (inducing neurite/axonal outgrowth) using the PC12 neuronal model. In the present study we extended the characterizations of the in vitro neurotropic effect of the derivative 3-(3-allyl-2-methylenecyclohexyl) propanoic acid (MCA-13) on dorsal root ganglia and spinal cord neuronal cultures and analyzed its safety properties using blood biochemistry and cell counting, acute toxicity evaluation in mice and different in vitro “off-target” pharmacological evaluations. This MCA derivative deserves further preclinical mechanistic pharmacological characterizations including therapeutic efficacy in in vivo animal models of polyneuropathies, toward development of a clinically relevant neurotropic drug.
ISSN:1948-7193
1948-7193
DOI:10.1021/acschemneuro.0c00255