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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The new antimycin antibiotics (I) are isolated along with several known analogues. They exhibit antifungal activity against Candida utilis. Compounds (Ia) and (Ib) form a 85:15 mixture which is inseparable by HPLC. -(HOSOTANI, N.; KUMAGAI, K.; NAKAGAWA, H.; SHIMATANI, T.; SAJI, I.; J. Antibiot. 58 (2005) 7, 460-467; Explor. Res. Group, Res. Div., Sumitomo Pharm. Co., Ltd., Takarazuka, Hyogo 665, Japan; Eng.) -M. Bohle 02-205