cn0c00255_si_001.pdf (1.9 MB)
Neurotropic activity and safety of methylene-cycloalkylacetate (MCA) derivative 3‑(3-allyl-2-methylenecyclohexyl) propanoic acid
journal contribution
posted on 2020-08-03, 19:41 authored by Adi Lahiani, Dikla Haham-Geula, David Lankri, Susan Cornell-Kennon, Erik M. Schaefer, Dmitry Tsvelikhovsky, Philip LazaroviciPolyneuropathy
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.