Atypical Angucyclinones with Ring Expansion and Cleavage from a Marine Streptomyces sp.

A unique ring C-expanded angucyclinone, oxemycin A (1), and seven new ring-cleavage derivatives (2-5 and 9-11) were isolated from the marine actinomycete Streptomyces pratensis KCB-132, together with eight known analogues (6-8 and 12-16). Their structures were elucidated by spectroscopic analyses, single-crystal X-ray diffractions, and NMR and ECD calculations. Among these atypical angucyclinones, compound 1 represented the first seven-membered ketoester in the angucyclinone family, which sheds light on the origin of fragmented angucyclinones with C-ring cleavage at C-12/C-12a in the Baeyer-Villiger hypothesis, such as 2-4, while the related "nonoxidized" analogues 5-8 seem to originate from a diverse pathway within the Grob fragmentation hypothesis. Additionally, we have succeeded in the challenging separation of elmenols E and F (12) into their four stereoisomers, which remained stable in aprotic solvents but rapidly racemized under protic conditions. Furthermore, the absolute configurations of LS1924 and its isomers (14 and 15) were assigned by ECD calculations for the first time. Surprisingly, these two bicyclic acetals are susceptible to hydrolysis in solution, resulting in fragmented derivatives 17 and 18 with C-ring cleavage between C-6a and C-7. Compared with ring C-modified angucyclinones, ring A-cleaved 11 was more active to multiple resistant "ESKAPE" pathogens with MIC values ranging from 4.7 to 37.5 µg/mL.

Strepyrazinone, a tricyclic diketopiperazine derivative with cytotoxicity from a marine-derived actinobacterium.

Strepyrazinone (1), a tricyclic diketopiperazine derivative with a carbon skeleton unprecedented in natural products, was isolated from the marine-derived Streptomyces sp. B223. Its structure was elucidated by spectroscopic analyses and electronic circular dichroism calculation. Compound 1 showed cytotoxic activity against HCT-116 cancer cell lines with an IC50 value of 0.34 µM.

NMDA receptor-mediated immediate Ser831 phosphorylation of GluR1 through CaMKIIalpha in rat hippocampus during early global ischemia.

The phosphorylation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors subunit GluR1 at Ser831 has been implicated in the regulation of AMPA receptors channel. In this paper, Ser831 phosphorylation of GluR1 in rat hippocampus was investigated, which significantly increased during early global ischemia. To further illustrate the underlying mechanisms, calcium/calmodulin-dependent kinase IIalpha (CaMKIIalpha) inhibitor 1-[N,O-bis-(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN62), CaM antagonist trifluoperazine (TFP), N-methyl-D-aspartate (NMDA) receptor antagonist dextromethorphan (DEX), AMPA receptor antagonist 6,7-dinitro-quinoxaline-2,3-(1H,4H)-dione (DNQX) and L-type voltage-gated Ca2+ channel (L-VGCC) blocker nifedipine (NIF), were respectively administrated to the rats 20 min prior to ischemia. The results showed that KN62, TFP and DEX significantly attenuated Ser831 phosphorylation of GluR1, while DNQX and NIF had no obvious effects. Consequently, the studies suggest that early global ischemia induced Ser831 phosphorylation of GluR1 may be closely associated with CaMKIIalpha and the NMDA receptor, while the immediate Ser831 phosphorylation of GluR1 may have been involved in pathogenic events after early global ischemia.