Xanthofulvin, a Novel Semaphorin Inhibitor Produced by a Strain of Penicillium

Kumagai, Kazuo; Hosotani, Nobuo; Kikuchi, Kaoru; Kimura, Tōru; Saji, Ikutaro

doi:10.7164/antibiotics.56.610

Cited by 52 publications

(42 citation statements)

References 11 publications

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“…52 In particular, SM-216289, a small-molecule inhibitor, showed inhibition of Sema3A functions, including growth cone collapse and chemorepulsion of neurite extension. 53,54 This compound acted on Sema3A by sterically inducing changes in its structure and hindering binding of NRP-1. Because Gal-1 not only exerts a…”

Section: Discussionmentioning

confidence: 99%

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

et al. 2014

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Following spinal cord injury (SCI), semaphorin 3A (Sema3A) prevents axonal regeneration through binding to the neuropilin-1 (NRP-1)/PlexinA4 receptor complex. Here, we show that galectin-1 (Gal-1), an endogenous glycan-binding protein, selectively bound to the NRP-1/PlexinA4 receptor complex in injured neurons through a glycan-dependent mechanism, interrupts the Sema3A pathway and contributes to axonal regeneration and locomotor recovery after SCI. Although both Gal-1 and its monomeric variant contribute to de-activation of microglia, only high concentrations of wild-type Gal-1 (which co-exists in a monomer-dimer equilibrium) bind to the NRP-1/PlexinA4 receptor complex and promote axonal regeneration. Our results show that Gal-1, mainly in its dimeric form, promotes functional recovery of spinal lesions by interfering with inhibitory signals triggered by Sema3A binding to NRP-1/PlexinA4 complex, supporting the use of this lectin for the treatment of SCI patients.

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Section: Discussionmentioning

confidence: 99%

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

et al. 2014

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“…4A). Furthermore, a higher concentration of SM-216289 was needed to inhibit the collapsing activity of Sema3A-AP, IC 50 ϭ 1.7 M. Thus there was a good correlation between the concentration of SM-216289 required to inhibit binding of Sema3A-AP and the IC 50 value for growth cone collapse by Sema3A-AP. The reason why Sema3-AP shows lower activity than native Sema3A is unclear.…”

Section: Sm-216289 Accelerates Nerve Regeneration In Vivo In a Rat Olmentioning

confidence: 78%

“…Strain SPF-3059 -The detailed procedure for the fermentation and purification of SM-216289 (50). Briefly, the fermentation broth of Penicillium sp.…”

Section: Methodsmentioning

confidence: 99%

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In Vitro and in Vivo Characterization of a Novel Semaphorin 3A Inhibitor, SM-216289 or Xanthofulvin

Kikuchi

Kishino

Konishi

et al. 2003

Journal of Biological Chemistry

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SM-216289 (xanthofulvin) isolated from the fermentation broth of a fungal strain, Penicillium sp. SPF-3059, was identified as a strong semaphorin 3A (Sema3A) inhibitor. Sema3A-induced growth cone collapse of dorsal root ganglion neurons in vitro was completely abolished in the presence of SM-216289 at levels less than 2 M (IC 50 ‫؍‬ 0.16 M). When dorsal root ganglion explants were co-cultured with Sema3A-producing COS7 cells in a collagen gel matrix, SM-216289 enabled neurites to grow toward the COS7 cells. SM-216289 diminished the binding of Sema3A to its receptor neuropilin-1 in vitro, suggesting a direct interference of receptor-ligand association. Moreover, our data suggest that SM-216289 interacted with Sema3A directly and blocked the binding of Sema3A to its receptor. We examined the efficacy of SM-216289 in vivo using a rat olfactory nerve axotomy model, in which strong Sema3A induction has been reported around regenerating axons. The regeneration of olfactory nerves was significantly accelerated by a local administration of SM-216289 in the lesion site, suggesting the involvement of Sema3A in neural regeneration as an inhibitory factor. SM-216289 is an excellent molecular probe to investigate the function of Sema3A, in vitro and in vivo, and may be useful for the treatment of traumatic neural injuries.

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“…Few examples are xanthopterin [30], xantholiptin [31], and xanthofulvin (30) and vinaxanthone (31) [32].…”

Section: Miscellaneous Xanthonementioning

confidence: 99%

Synthesis and Biological Properties of Pharmaceutically Important Xanthones and Benzoxanthone Analogs: A Brief Review.

Bedi

Gupta

Pramanik

2018

Asian J Pharm Clin Res

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Xanthones are one of the biggest classes of compounds in natural product chemistry. A number of xanthones have been isolated from natural sources of higher plants such as fungi, ferns, and lichens. Synthetic analogs of xanthones have shown a large number of pharmacological properties such as antioxidant, anti-inflammatory, antidiabetics, antihistamine, antitumoral, antiulcer, and algicidal. Moreover, they also find usages in photodynamic therapy, laser technology, and dyes. This review lays stress on various solvents, catalyst and synthetic route for synthesis of xanthones, benzoxanthones analogs. The review has also focused on the classifications of xanthone as well as extensively studied biological properties of the xanthones and benzoxanthones analogs.

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Xanthofulvin, a Novel Semaphorin Inhibitor Produced by a Strain of Penicillium

Cited by 52 publications

References 11 publications

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

In Vitro and in Vivo Characterization of a Novel Semaphorin 3A Inhibitor, SM-216289 or Xanthofulvin

Synthesis and Biological Properties of Pharmaceutically Important Xanthones and Benzoxanthone Analogs: A Brief Review.

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