Characterization of a New Antienterovirus D68 Compound Purified from Avocado.

One of the major challenges in development of antienterovirus (EV) drugs is in the safety of the drug. Here, we attempted to identify anti-EV compounds from an edible plant extract library and found potent antienterovirus D68 (EV-D68) activity in avocado (Persea americana). The purified identity is determined as 2R,4R-(12Z,15Z)-heneicosa-12,15-diene-1,2,4-triol, named avoenin. Avoenin shows an EC50 of 2.0 µM for EV-D68 (Fermon) infection with CC50 of >150 µM in RD cells by targeting the uncoating step of EV-D68 infection. Resistant mutations of EV-D68 (VP3-V24I, S173P, and S180G) to avoenin confer cross-resistance to pleconaril, an uncoating inhibitor of EV-D68. The inhibitory effect of avoenin is substantially specific to EV-D68 among the EVs. This work reveals avoenin as the identity of anti-EV-D68 activity in avocado and offers insights into development of a novel and effective strategy to overcome EV-D68 infection and its related respiratory diseases.

Botanical origin and chemical constituents of commercial Saposhnikoviae radix and its related crude drugs available in Shaanxi and the surrounding regions.

Saposhnikoviae radix (SR) is described in the Japanese Pharmacopoeia as a crude drug derived from the root of Saposhnikovia divaricata Schischkin (Umbelliferae). According to Flora of China, the root of Peucedanum ledebourielloides K. F. Fu is used as a regional substitute for SR. Therefore, we surveyed the botanical origin of the drug used in China, especially Shaanxi and the surrounding regions, through nucleotide sequence analysis of the internal transcribed spacer region of rDNA. As a result, several samples from Shaanxi () and Shanxi () provinces were identified as Peucedanum ledebourielloides. To prevent this substitute from being distributed as genuine SR, we developed a thin-layer chromatography analysis condition to enable a specific compound of this species to be easily detected. The specific compound was identified as xanthalin, based on 1D- and 2D-NMR and high-resolution mass spectrometry data. The established TLC conditions were as follows-extraction solvent, n-hexane; applied volume, 5 µL; chromatographic support, silica gel; developing solvent, n-hexane:ethyl acetate:acetic acid (20:10:1); developing length, 7 cm; detection, UV (365 nm); R f value, 0.4 (blue fluorescence; xanthalin).

Identification of ten KB425796-A congeners from Paenibacillus sp. 530603 using an antifungal assay against Aspergillus fumigatus in combination with micafungin.

The discovery and characterization of natural congeners is one approach for understanding the relationship between chemical structure and biological function. We recently isolated the novel antifungal metabolite KB425796-A produced by the recently isolated bacterium Paenibacillus sp. 530603. On the basis of morphological changes of Aspergillus fumigatus induced by KB425796-A in combination with micafungin, we developed a highly sensitive screening method for the specific detection of KB425796-A congeners. Using this method, we isolated ten congeners of KB425796-A, named KB425796-B, -C, -D, -E, -F, -G, -H, -I, -J and -K, which exhibited diverse antifungal potencies against A. fumigatus. One of the most potent congeners, KB425796-C, had antifungal activities against several micafungin-resistant infectious fungi. KB425796-C can be a potential drug candidate for treating micafungin-resistant fungal infections.

KB425796-A, a novel antifungal antibiotic produced by Paenibacillus sp. 530603.

The novel antifungal macrocyclic lipopeptidolactone, KB425796-A (1), was isolated from the fermentation broth of bacterial strain 530603, which was identified as a new Paenibacillus species based on morphological and physiological characteristics, and 16S rRNA sequences. KB425796-A (1) was isolated as white powder by solvent extraction, HP-20 and ODS-B column chromatography, and lyophilization, and was determined to have the molecular formula C79H115N19O18. KB425796-A (1) showed antifungal activities against Aspergillus fumigatus and the micafungin-resistant infectious fungi Trichosporon asahii, Rhizopus oryzae, Pseudallescheria boydii and Cryptococcus neoformans.

Naphthalecin, a novel antibiotic produced by the anaerobic bacterium, Sporotalea colonica sp. nov.

A novel antibiotic naphthalecin was purified and isolated from the cells of an anaerobic bacterium isolated from a soil sample. This antibiotic contained a naphthalene moiety, so named as naphthalecin, and showed antibacterial activity against gram positive species. The producing strain, an obligate anaerobe, was identified as a new species of the genus Sporotalea. Identification of the bacterium, cultivation, purification, structure determination, and antibacterial activity are shown.

FR207944, an antifungal antibiotic from Chaetomium sp. no. 217 I. Taxonomy, fermentation, and biological properties.

An antifungal antibiotic, FR207944, was isolated from the culture broth of a fungal strain Chaetomium sp. no. 217. FR207944 is a triterpene glucoside with antifungal activity against Aspergillus fumigatus and Candida albicans. Specifically, FR207944 exhibits in vitro and in vivo antifungal activity against A. fumigatus. The effects of FR207944 on the morphology of A. fumigatus were shown to be similar to those of FR901379, a known 1,3-beta-glucan synthase inhibitor. The MECs of FR207944 against A. fumigatus FP1305 and C. albicans FP633 in micro-broth dilution test were 0.039 and 1.6 mug/ml respectively. FR207944 showed good potency by subcutaneous injection and oral administration against A. fumigatus in a murine systemic infection model, with ED(50)s of 5.7 and 17 mg/kg respectively.

FR227244, a novel antifungal antibiotic from Myrothecium cinctum No. 002 Taxonomy, fermentation, isolation and physico-chemical properties.

A novel antifungal antibiotic, FR227244, was isolated from the culture broth of a fungal strain No. 002. The strain was identified as Myrothecium cinctum from morphological and physiological characteristics. This compound was isolated from the culture broth by solvent extraction, HP-20 and YMC ODS gel column chromatographies, and n-hexane precipitation. FR227244 is a white powder which melts at 210 to approximately 211 degrees C and possesses the molecular formula C38H58O11. FR227244 is a novel triterpene glycoside with antifungal activity against Aspergillus fumigatus. The effects of FR227244 on the morphology of A. fumigatus were shown to be similar to those of FR901379 which is a known 1,3-beta-glucan synthase inhibitor.