Hippocampal and cortical neuronal growth mediated by the small molecule natural product clovanemagnolol

• Published in: Bioorganic & medicinal chemistry letters Vol. 21; no. 16; pp. 4808 - 4812
• Main Authors: Khaing, Zin, Kang, Danby, Camelio, Andrew M., Schmidt, Christine E., Siegel, Dionicio
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.08.2011; Elsevier
• Subjects: Animals; bark; Biological and medical sciences; Biological Factors - chemical synthesis; Biological Factors - chemistry; Biological Factors - pharmacology; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - embryology; Clovanemagnolol; Cortical; dose response; Dose-Response Relationship, Drug; Growth factors; growth promotion; Hippocampal; Hippocampus - cytology; Hippocampus - embryology; Magnolia; Magnolia macrophylla; Medical sciences; medicine; Molecular Conformation; Molecular Weight; Natural products; Neuronal; neurons; Neurons - cytology; Neurons - drug effects; Pharmacology. Drug treatments; Phenols - chemical synthesis; Phenols - chemistry; Phenols - pharmacology; Rats; Sesquiterpenes - chemical synthesis; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology; Small molecule; Stereoisomerism; Structure-Activity Relationship; Synthesis; trees; Synthesis; Natural products; Hippocampal; Clovanemagnolol; Small molecule; Neuronal; Growth factors; Cortical; Embryo; Growth; Saturated compound; Nervous system; Sesquiterpenes; Secondary alcohol; Chemical synthesis; Terpenoid; Ether; Natural compound; Tricyclic compound; In vitro; Biological activity; Neurotrophic factor; Neuron; Biphenyl derivatives; Phenols; Hippocampus; Growth factor
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.06.054

The use of small molecule surrogates of growth factors that directly or indirectly promote growth represents an attractive approach to regenerative medicine. With synthetic access to clovanemagnolol, a small molecule initially isolated from the bark of the Bigleaf Magnolia tree, we have examined the small molecule’s ability to promote growth of embryonic hippocampal and cortical neurons in serum-free medium. Comparisons with magnolol, a known promoter of growth, reveals that clovanmagnolol is a potent neurotrophic agent, promoting neuronal growth at concentrations of 10nM. In addition, both clovanemagnolol and magnolol promote growth through a biphasic dose response.