期刊
ACS CHEMICAL NEUROSCIENCE
卷 9, 期 4, 页码 691-698出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.7b00473
关键词
Methylene-cycloalkylacetate; pharmacophore; neurotropic activity; D-f; PC12 cultures; NGF
资金
- David R. Bloom Center for Pharmacy
- Dr. Adolf and Klara Brettler Center for Research in Molecular Pharmacology and Therapeutics at the Hebrew University of Jerusalem, Israel
- Yissum-HUJI
- State of Lower Saxony, Hannover, Germany
One of the main symptoms in degenerative diseases is death of neuronal cell followed by the loss of neuronal pathways. In neuronal cultures, neurite outgrowths are cell sprouts capable of transforming into either axons or dendrites, to further form functional neuronal synaptic connections. Such connections have an important role in brain cognition, neuronal plasticity, neuronal survival, and regeneration. Therefore, drugs that stimulate neurite outgrowth may be found beneficial in ameliorating neural degeneration. Here, we establish the existence of a unique family of methylene-cycloalkylacetate-based molecules (MCAs) that interface with neuronal cell properties and operate as acceptable pharmacophores for a novel neurotropic (neurite outgrowth inducing) lead compounds. Using an established PC12 cell bioassay, we investigated the neurotropic effect of methylene-cycloalkylacetate compounds by comparison to NGF, a known neurotropic factor. Micrographs of the cells were collected by using a light microscope camera, and digitized photographs were analyzed for compound -induced neurotropic activity using an NIH image protocol. The results indicate that the alkene element, integrated within the cycloalkylacetate core, is indispensable for neurotropic activity. The discovered lead compounds need further mechanistic investigation and may be improved toward development of a neurotropic drug.
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