New azasteroidal antifungal antibiotics from Geotrichum flavo-brunneum. III. Biological activity. (1/15)
The A25822 antibiotic complex consists of seven biologically active factors. A comparative study of these factors determined that factor B possessed the greatest antifungal activity. The minimal inhibitory concentration of A25822B against isolates of Candida albicans was less than 0.3 similar to 5.0 mug/ml, Trichophyton mentagrophytes was inhibited at less than 0.0312 mug/ml. Other pathogenic fungi such as Cryptococcus neoformans, Histoplasma capsulatum, Blastomyces dermatitidis, Sporotrichum schenckii, and Microsporium gypseum were very susceptible to A25822B. Only limited antibacterial activity of A25822B was found. Parenteral or oral administration of 50 mg/kg of A25822B significantly extended the average survival time of mice infected with C. albicans. Doses of 20 mg/kg of A25822B caused a greater than ten-fold reduction in the number of Candida cells recovered from kidneys of infected mice. A solution of 0.5% or 0.25% A25822B applied topically was effective against an experimental dermatophyte infection on guinea pigs. A peak blood level of 3 mug/ml was achieved in mice following a 100 mg/kg dose of A25822B. Combination of A25822B with a polyene antibiotic in vitro showed antagonism. (+info)New azasteroidal antifungal antibotics from Geotrichum flavo-brunneum. I. Discovery and fermentation studies. (2/15)
Although Geotrichum species occur ubiquitously, antibiotic production by members of this genus has not previously been reported. The antibiotic complex designated A25822, consisting of one major and six minor structurally-related components active primarily against Candida and Trichophyton, represents a new family of naturally-occurring compounds. Approximately 90% of the antibiotic activity synthesized remained associated with the fungal cell mass, from which it was recovered by multiple methanolic extractions for quantitation. Antibiotic production was enhanced by tryptophan, iron, zinc, and high levels of dextrin. (+info)New azasteroidal antifungal antibiotics from Geotrichum flavo-brunneum. II. Isolation and characterization. (3/15)
A novel group of antibiotics, comprising microbiologically-active structurally-related factors A25822A, B, D, H, L, M and N, produced by culturing Geotrichum flavo-brunneum NRRL 3862 under submerged aerobic fermentation conditions was isolated by extraction. The individual factors were separated and purified by chromatography and crystallization. The major factor, A25822B, a 15-aza-24-methylene-D-homocholestadiene is a white crystalline compound, C25H45NO. The antibiotics are highly active against fungi and marginally active against bacteria. (+info)Scalaradial inhibition of epidermal growth factor receptor-mediated Akt phosphorylation is independent of secretory phospholipase A2. (4/15)
The marine natural product 12-epi-scalaradial (SLD) is a specific secretory phospholipase A(2) (sPLA(2)) inhibitor. However, little is known about whether this compound has other pharmacological effects. Here, we revealed a novel effect of SLD on epidermal growth factor receptor (EGFR)-mediated Akt phosphorylation. SLD dose- and time-dependently inhibited epidermal growth factor (EGF)-stimulated Akt phosphorylation, which is required for Akt activation. SLD also blocked the EGF-stimulated membrane translocation of 3-phosphoinositide-dependent protein kinase 1 and inhibited phosphatidylinositol 3-kinase activity. This inhibition is specific for SLD because other phospholipase inhibitors, including sPLA(2) inhibitor thioetheramide-phosphatidylcholine, cytosolic PLA(2) inhibitor arachidonyl trifluoromethyl ketone, cytosolic PLA(2) and Ca(2+)-independent PLA(2) inhibitor methyl arachidonyl fluorophosphonate, phospholipase C inhibitor U73122, and cyclooxygenases inhibitor indomethacin, failed to inhibit EGF-stimulated Akt phosphorylation. Furthermore, arachidonic acid, the main sPLA(2)-catalyzed metabolite, was not able to rescue SLD inhibition of EGF-stimulated Akt phosphorylation. Overexpression of group IIA or group X sPLA(2) did not reverse the inhibitory effect of SLD on Akt phosphorylation, either. Our results demonstrate that SLD inhibits EGFR-mediated Akt phosphorylation, and this novel effect of SLD is independent of sPLA(2). (+info)Biphasic regulation of extracellular signal-regulated kinases by scalaradial, a secretory phospholipase A(2) inhibitor. (5/15)
The marine natural product scalaradial (SLD) is a potent inhibitor of secretory phospholipase A(2) (sPLA(2)). Our previous work has demonstrated that SLD inhibits epidermal growth factor receptor-mediated Akt phosphorylation, and this effect is independent of sPLA(2). Here we report the role of SLD in extracellular signal-regulated kinase (ERK)1/2 activation. SLD inhibited ERK1/2 phosphorylation within the first 15 min (early inhibition), then stimulated ERK1/2 phosphorylation after 15 min of SLD treatment (late stimulation) in BEL-7402 cells, displaying biphasic regulatory features. Other PLA(2) inhibitors such as the cytosolic and Ca(2+)-independent PLA(2) inhibitor methyl arachidonyl fluorophosphonate, and another sPLA(2) inhibitor, thioetheramide-phosphatidylcholine, only transiently inhibited ERK1/2 phosphorylation and did not display the stimulatory effect. The early inhibition of ERK1/2 phosphorylation by SLD was reversed by the PLA(2) metabolite arachidonic acid, while the late stimulation was abrogated by constitutively active myristolated-Akt. Furthermore, SLD dose- and time-dependently inhibited the phosphorylation of Raf-1 on Ser 259, which is an established event by which Akt inhibits ERK1/2 activation. Taken together, these data demonstrate a biphasic regulation of ERK1/2 phosphorylation by SLD in a time-dependent manner, i.e., early inhibition and late stimulation. The early inhibition of ERK1/2 phosphorylation is mediated by sPLA(2), at least in part, and the late stimulation is effected through SLD inhibition of Akt. These findings provide further insight into the mechanisms underlying the pharmacological effect of SLD. (+info)Group V phospholipase A2-derived lysophosphatidylcholine mediates cyclooxygenase-2 induction in lipopolysaccharide-stimulated macrophages. (6/15)
Activation of macrophages and macrophage cell lines by bacterial LPS elicits a delayed phase of PG biosynthesis that appears to be entirely mediated by cyclooxygenase-2 (COX-2). In previous work, we found that a catalytically active group V secreted phospholipase A(2) (sPLA(2)-V) was required for COX-2 induction, but the nature of the sPLA(2)-V metabolite involved was not defined. In this study, we identify lysophosphatidylcholine (lysoPC) as the sPLA(2)-V downstream mediator involved in COX-2 induction by LPS-stimulated macrophages. Inhibition of sPLA(2)-V by RNA interference or by the cell-permeable compound scalaradial blocked LPS-induced COX-2 expression, and this inhibition was overcome by incubating the cells with a nonhydrolyzable lysoPC analog, but not by arachidonic acid or oleic acid. Moreover, inhibition of sPLA(2)-V by scalaradial also prevented the activation of the transcription factor c-Rel, and such an inhibition was also selectively overcome by the lysoPC analog. Collectively, these results support a model whereby sPLA(2)-V hydrolysis of phospholipids upon LPS stimulation results in lysoPC generation, which in turn regulates COX-2 expression by a mechanism involving the transcriptional activity of c-Rel. (+info)Synthesis and structure revision of nakiterpiosin. (7/15)
(+info)Chemical and biological studies of nakiterpiosin and nakiterpiosinone. (8/15)
(+info)I'm sorry for any confusion, but the term "Homosteroids" does not appear to be a recognized or established term in the field of medicine or physiology, and I could not find any relevant information about it. It's possible that there might be a spelling mistake or a misunderstanding of the term. If you have more context or information, I would be happy to try and help further.
I'm sorry for any confusion, but "Homosteroids" is not a recognized term in medical or scientific literature. It seems like there may be a misunderstanding or a typo in the term you're looking for. Steroids, however, are organic compounds that include several types of hormones and signaling molecules. If you have any other terms or concepts you would like me to explain, please let me know!
Steroid
Ingestion of these C-nor-D-homosteroids results in birth defects in lambs: cyclopia from cyclopamine and leg deformity from ... Wolfing J (2007). "Recent developments in the isolation and synthesis of D-homosteroids and related compounds". Arkivoc. 2007 ( ... Norsteroids (nor-, L. norma; "normal" in chemistry, indicating carbon removal) and homosteroids (homo-, Greek homos; "same", ...
Biomimetic synthesis
... and homosteroids), via C-13 atom migration Heathcock synthesis of squalene-derived daphniphylline-type alkaloids, via ... via Nicolaou approach Merck synthesis of nakiterpiosin-type C-nor-D-homosteroids, e.g., Structural: Cleaved, contracted, and ...