Neurotropic activity and safety of methylene-cycloalkylacetate (MCA) derivative 3-(3-allyl-2-methylenecyclohexyl) propanoic acid. Lahiani, A., Hacham-Geula, D., Lankri, D., Cornell-Kennon, S., Schaefer, E. M., Tsvelikhovsky, D., Lazarovici, P.
ACS Chem. Neurosci. 2020, 11, 17, 2577-2589.
The Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
AssayQuant Technologies Inc. 260 Cedar Hill Street, Marlboro, MA 01752, USA
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 allylmethylene-cyclohexyl-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.
Lahiani, A., Hacham-Geula, D., Lankri, D., Cornell-Kennon, S., Schaefer, E. M., Tsvelikhovsky, D., Lazarovici, P. ACS Chem. Neurosci. 2020, 11, 17, 2577-89.
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