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

Adi Lahiani, Dikla Haham-Geula, David Lankri, Susan Cornell-Kennon, Erik M. Schaefer, Dmitry Tsvelikhovsky*, Philip Lazarovici

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)2577-2589
Number of pages13
JournalACS Chemical Neuroscience
Volume11
Issue number17
DOIs
StatePublished - 2020

Bibliographical note

Funding Information:
D.T. holds the Gerald Heller Chair in Pharmaceutical Chemistry, gratefully acknowledge the Israel Science Foundation - ISF Research Grant (367/18) for the financial support. This work was also supported in part by the Hebrew University of Jerusalem - Yissum Intramural Research Funds. PL holds the Jacob Gitlin Chair in Physiology and is affiliated and supported by David R. Bloom Center for Pharmacy, Dr. Adolf and Klara Brettler Center for Research in Molecular Pharmacology and Therapeutics, and the Grass Center for Drug Design and Synthesis of Novel Therapeutics at the Hebrew University of Jerusalem, Israel.

Publisher Copyright:
© 2020 American Chemical Society

Keywords

  • DRG
  • Enzyme
  • GPCR
  • Kinome
  • Methylene-cycloalkylacetate
  • Neurotropic activity
  • Off-target
  • PC12
  • PGE
  • Safety
  • Spinal cord neuron
  • Transporter

Fingerprint

Dive into the research topics of 'Neurotropic activity and safety of methylene-cycloalkylacetate (MCA) derivative 3-(3-allyl-2-methylenecyclohexyl) propanoic acid'. Together they form a unique fingerprint.

Cite this