Caixia Chen

Abyssomicins from the South China Sea deep-sea sediment Verrucosispora sp.: natural thioether michael addition adducts as antitubercular prodrugs

Tuberculosis (TB) is a leading cause of death in the world today, and is exacerbated by the prevalence of multi- (MDR-TB), extensively (XDR-TB), and totally (TDR-TB) drug resistant strains. Despite the threat to human health, existing frontline TB therapeutics remain constrained to a handful of vintage antibiotics prescribed in a combinatorial format to achieve efficacy. The current shortfall in antitubercular drugs demands urgent attention, to develop new antibiotics effective against all strains of tuberculosis.

Trichodermaketones A-D and 7-O-Methylkoninginin D from the Marine Fungus Trichoderma koningii

Five new polyketide derivatives, 7-O-methylkoninginin D (1) and trichodermaketones A-D (2-5), together with four known compounds, koninginins A, D, E, and F, were isolated from the marine-derived fungus Trichoderma koningii. Trichodermaketones A (2) and B (3) are unprecedented polyketides with a bistetrafuran-containing tricyclic skeleton. The chemical structures and absolute configurations of compounds 1-5 were elucidated by comparing with literature data and extensive spectroscopic methods, including 2D NMR and CD spectroscopic analysis. Compounds 1-5 were evaluated for action against bacteria and fungi and for synergistic antifungal activity. Compound 2 showed synergistic antifungal activity against Candida albicans with 0.05 microg/mL ketoconazole.

Verrucisidinol and Verrucosidinol Acetate, Two Pyrone-Type Polyketides Isolated from a Marine Derived Fungus, Penicillium aurantiogriseum

The new secondary metabolites verrucosidinol (1) and its derivative verrucosidinol acetate (2), together with a potent neurotoxin verrucosidin (3), a congener norverrucosidin (4) and a mixture of two known phytotoxic metabolites terrestric acids (5 and 6), were isolated from the marine derived fungus Penicillium aurantiogriseum. Verrucosidinol has a ring-opened ethylene oxide moiety in the polyene α-pyrone skeleton, and verrucosidinol acetate is its acetate derivative. The chemical structures were determined by comparing with literature data and a combination of spectroscopic techniques, including high resolution mass spectrum and two-dimentional nuclear magnetic resonance spectroscopic analysis.

Quinazolin-4-one Coupled with Pyrrolidin-2-iminium Alkaloids from Marine-Derived Fungus Penicillium aurantiogriseum

Three new alkaloids, including auranomides A and B (1 and 2), a new scaffold containing quinazolin-4-one substituted with a pyrrolidin-2-iminium moiety, and auranomide C (3), as well as two known metabolites auranthine (4) and aurantiomides C (5) were isolated from the marine-derived fungus Penicillium aurantiogriseum. The chemical structures of compounds 1–3 were elucidated by extensive spectroscopic methods, including IR, HRESIMS and 2D NMR spectroscopic analysis. The absolute configurations of compounds 1–3 were suggested from the perspective of a plausible biosynthesis pathway. Compounds 1–3 were subjected to antitumor and antimicrobial screening models. Auranomides A–C exhibited moderate cytotoxic activity against human tumor cells. Auranomides B was the most potent among them with an IC50 value of 0.097 μmol/mL against HEPG2 cells.

Benzophenone C-glucosides and gallotannins from mango tree stem bark with broad-spectrum anti-viral activity

The high mutation rate of RNA viruses has resulted in limitation of vaccine effectiveness and increased emergence of drug-resistant viruses. New effective antivirals are therefore needed to control of the highly mutative RNA viruses. The n-butanol fraction of the stem bark of Mangifera indica exhibited inhibitory activity against influenza neuraminidase (NA) and coxsackie virus 3C protease. Bioassay guided phytochemical study of M. indica stem bark afforded two new compounds including one benzophenone C-glycoside (4) and one xanthone dimer (7), together with eleven known compounds. The structures of these isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Anti-influenza and anti-coxsackie virus activities were evaluated by determining the inhibition of anti-influenza neuraminidase (NA) from pandemic A/RI/5+/1957 H2N2 influenza A virus and inhibition of coxsackie B3 virus 3C protease, respectively. The highest anti-influenza activity was observed for compounds 8 and 9 with IC50 values of 11.9 and 9.2μM, respectively. Compounds 8 and 9 were even more potent against coxsackie B3 virus 3C protease, with IC50 values of 1.1 and 2.0μM, respectively. Compounds 8 and 9 showed weak cytotoxic effect against human hepatocellular carcinoma and human epithelial carcinoma cell lines through MTT assay.

Effects of 14-Alpha-Lipoyl Andrographolide on Quorum Sensing in Pseudomonas aeruginosa

ABSTRACT In Pseudomonas aeruginosa, the quorum-sensing (QS) system is closely related to biofilm formation. We previously demonstrated that 14-alpha-lipoyl andrographolide (AL-1) has synergistic effects on antibiofilm and antivirulence factors (pyocyanin and exopolysaccharide) of P. aeruginosa when combined with conventional antibiotics, while it has little inhibitory effect on its growth. However, its molecular mechanism remains elusive. Here we investigated the effect of AL-1 on QS systems, especially the Las and Rhl systems. This investigation showed that AL-1 can inhibit LasR–3-oxo-C12-homoserine lactone (HSL) interactions and repress the transcriptional level of QS-regulated genes. Reverse transcription (RT)-PCR data showed that AL-1 significantly reduced the expression levels of lasR, lasI, rhlR, and rhlI in a dose-dependent manner. AL-1 not only decreased the expression level of Psl, which is positively regulated by the Las system, but also increased the level of secretion of ExoS, which is negatively regulated by the Rhl system, indicating that AL-1 has multiple effects on both the Las and Rhl systems. It is no wonder that AL-1 showed synergistic effects with other antimicrobial agents in the treatment of P. aeruginosa infections.

Nivetetracyclates A and B: Novel Compounds Isolated from Streptomyces niveus

A high-throughput screening of a microbial natural product library led to the discovery of two novel compounds named nivetetracyclates A and B (1 and 2), which were produced by Streptomyces niveus designated as LS2151. The backbone of the compounds contains a hydrotetracyclate not previously reported from a natural source. The structures of the compounds were elucidated by spectroscopic methods. The nivetetracyclates exhibited activity against human HeLa cells.