“…16 , significantly enhanced the neurite outgrowth of NGF-mediated PC12 cells at concentrations ranging from 5 to 40 μM [ 119 , 120 ]. A good synthetic achievement of neovibsanin B was accomplished by Imagawa et al [ 121 ], who then extended their synthetic efforts to structure–activity relationship studies, resulting in elucidation of the minimum structure required for displaying neurite outgrowth activity in NGF-mediated PC12 cells (compound 56 ) [ 122 ]. Fig.…”
Section: Miscellaneous Natural Products With Neurotrophic Effectsmentioning
Neurotrophic factors, now termed neurotrophins, which belong to a class of polypeptidyl agents, have been shown to potentially be beneficial for the treatment of neurodegenerative diseases such as Alzheimer's disease, because endogenous neurotrophic factors (NGF, BDNF, NT3, NT4) have been recognized to play critical roles in the promotion of neurogenesis, differentiation, and neuroprotection throughout the development of the central nervous system. However, high-molecular weight proteins are unable to cross the blood-brain barrier and are easily decomposed by peptidase under physiological conditions. To address this issue, small molecules that can mimic the functions of neurotrophic factors would be promising alternatives for the treatment of neurodegenerative disease. We have continued to search for natural products having typical neurotrophic properties, which can cause neurogenesis, enhance neurite outgrowth, and protect neuronal death using three cellular systems (PC12, rat cortical neurons, and MEB5 cells). In this review, we summarize the neurotrophic activities and synthesis of dimeric isocuparane-type sesquiterpenes from the liverwort, Mastigophora diclados, the mechanism of neurotrophic neolignans, magnolol, honokiol and their sesquiterpene derivatives, and introduce unique neurotrophin-mimic natural products, including seco-prezizaane-type sesquiterpenes from the Illicium species, vibsane-type diterpenes from Viburnum awabuki, and miscellaneous natural products with neurotrophic effects discovered by us.
“…16 , significantly enhanced the neurite outgrowth of NGF-mediated PC12 cells at concentrations ranging from 5 to 40 μM [ 119 , 120 ]. A good synthetic achievement of neovibsanin B was accomplished by Imagawa et al [ 121 ], who then extended their synthetic efforts to structure–activity relationship studies, resulting in elucidation of the minimum structure required for displaying neurite outgrowth activity in NGF-mediated PC12 cells (compound 56 ) [ 122 ]. Fig.…”
Section: Miscellaneous Natural Products With Neurotrophic Effectsmentioning
Neurotrophic factors, now termed neurotrophins, which belong to a class of polypeptidyl agents, have been shown to potentially be beneficial for the treatment of neurodegenerative diseases such as Alzheimer's disease, because endogenous neurotrophic factors (NGF, BDNF, NT3, NT4) have been recognized to play critical roles in the promotion of neurogenesis, differentiation, and neuroprotection throughout the development of the central nervous system. However, high-molecular weight proteins are unable to cross the blood-brain barrier and are easily decomposed by peptidase under physiological conditions. To address this issue, small molecules that can mimic the functions of neurotrophic factors would be promising alternatives for the treatment of neurodegenerative disease. We have continued to search for natural products having typical neurotrophic properties, which can cause neurogenesis, enhance neurite outgrowth, and protect neuronal death using three cellular systems (PC12, rat cortical neurons, and MEB5 cells). In this review, we summarize the neurotrophic activities and synthesis of dimeric isocuparane-type sesquiterpenes from the liverwort, Mastigophora diclados, the mechanism of neurotrophic neolignans, magnolol, honokiol and their sesquiterpene derivatives, and introduce unique neurotrophin-mimic natural products, including seco-prezizaane-type sesquiterpenes from the Illicium species, vibsane-type diterpenes from Viburnum awabuki, and miscellaneous natural products with neurotrophic effects discovered by us.
“…More recently, a fluorescently labeled and structurally simplified neovibsanin analogue was observed to accumulate around the outer edge prominences of the PC-12 cells. [231] …”
Neurodegenerative diseases and spinal cord injury affect approximately 50 million people worldwide, bringing the total healthcare cost to over 600 billion dollars per year. Nervous system growth factors, that is, neurotrophins, are a potential solution to these disorders, since they could promote nerve regeneration. An average of 500 publications per year attests to the significance of neurotrophins in biomedical sciences and underlines their potential for therapeutic applications. Nonetheless, the poor pharmacokinetic profile of neurotrophins severely restricts their clinical use. On the other hand, small molecules that modulate neurotrophic activity offer a promising therapeutic approach against neurological disorders. Nature has provided an impressive array of natural products that have potent neurotrophic activities. This Review highlights the current synthetic strategies toward these compounds and summarizes their ability to induce neuronal growth and rehabilitation. It is anticipated that neurotrophic natural products could be used not only as starting points in drug design but also as tools to study the next frontier in biomedical sciences: the brain activity map project.
“…[229] Über die erste Totalsynthese von (AE)-Neovibsanin B (263) berichteten Imagawa, Nishizawa et al [229b] Sie beruht auf der Bildung des Lactons 265 durch intramolekulare Diels-Alder-Reaktion, [72] Neurotrophe Naturstoffe Angewandte Chemie fluoreszenzmarkierten und strukturell vereinfachten Neovibsanin-Analogons um die Vorsprünge am Außenrand der PC-12-Zellen nachgewiesen. [231] 2.11. Weitere neurotrophe Naturstoffe Außer den bisher genannten Naturstoffen hat die Natur noch weitere faszinierende niedermolekulare Verbindungen hervorgebracht, die zwar strukturell unterschiedlich komplex sind, aber ähnliche hochinteressante neurotrophe Aktivität haben.…”
Neurodegenerative Erkrankungen und Rückenmarksverletzungen betreffen weltweit etwa 50 Millionen Menschen und verursachen Gesundheitskosten von insgesamt mehr als 600 Milliarden Dollar pro Jahr. Nervenwachstumsfaktoren, d. h. Neurotrophine, sind potenzielle Therapeutika für diese Erkrankungen, denn sie können die Regeneration von Nerven fördern. Durchschnittlich 500 Publikationen jährlich belegen die Bedeutung der Neurotrophine in den biomedizinischen Wissenschaften und ihr Potenzial für therapeutische Anwendungen. Allerdings ist die klinische Verwendung von Neurotrophinen wegen ihres schlechten pharmakokinetischen Profils stark eingeschränkt. Niedermolekulare Verbindungen, die die neurotrophe Aktivität modulieren, bieten hingegen einen vielversprechenden Therapieansatz bei neurologischen Erkrankungen. Die Natur hat für eine beeindruckende Zahl von Naturstoffen mit starken neurotrophen Wirkungen gesorgt. Die aktuellen Strategien zur Synthese dieser Verbindungen sowie deren Fähigkeit, das Wachstum und die Erneuerung von Nervenzellen zu induzieren, bilden den Schwerpunkt dieses Aufsatzes. Es ist davon auszugehen, dass neurotrophe Naturstoffe nicht nur als Leitstrukturen in der Wirkstoffentwicklung genutzt werden können, sondern auch für das nächste große Projekt der Biomedizin: die Kartierung der Hirnaktivität (BAM, Brain Activity Map).
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