Synthesis of novel tetrandrine derivatives and their inhibition against NSCLC A549 cells.

A series of novel tetrandrine (Tet) derivatives were synthesized through Suzuki -Miyaura reaction and evaluated for their cytotoxicity against human non-small cell lung carcinoma (NSCLC) A549 cells. Interestingly, most of derivatives showed similar cytotoxicity to Tet against NSCLC A549 cells, and particularly, compounds Y5, Y6, Y9 and Y11 showed the most significant cytotoxic effects with IC50 values ranging from 3.87 to 4.66 mM. The present study is expected to contribute to the future design of more effective anticancer agents in lung cancer chemotherapy.

5-Aminosalicylic acid inhibits inflammatory responses by suppressing JNK and p38 activity in murine macrophages.

CONTEXT: 5-Aminosalicylic acid (5-ASA), as an anti-inflammatory drug, has been extensively used for the treatment of mild to moderate active ulcerative colitis (UC), but the possible mechanisms of action remain unclear. OBJECTIVE: To investigate the effects of 5-ASA on the production of inflammatory mediators by murine macrophages stimulated with lipopolysaccharide (LPS), and determine the underlying pharmacological mechanism of action. MATERIALS AND METHODS: The levels of nitric oxide (NO) and interleukin-6 (IL-6) were measured by Varioskan Flash and IL-6 Enzyme-Linked Immunosorbent Assay sets. Real time quantitative polymerase chain reaction was used to determine the level of induced nitric oxide synthase (iNOS). The effects of 5-ASA on iNOS, the c-Jun N-terminal kinases (JNKs), p38 and nuclear factor (NF)-κB signaling pathways were examined using western blotting. RESULTS: 5-ASA suppressed the production of NO and IL-6, and also decreased the expression of iNOS in LPS-induced RAW264.7 cells. 5-ASA inhibited the phosphorylation of JNKs and p38, but did not block NF-κB activation at all doses tested. DISCUSSION AND CONCLUSION: The results indicated that the anti-inflammatory effect of 5-ASA was mainly regulated by the inhibition of the JNKs, p38 pathways rather than NF-κB pathway. Further research is required to clarify the detailed mechanism of the action.

Design and synthesis of new tetrandrine derivatives and their antitumor activities.

A series of tetrandrine derivatives were designed and synthesized using Suzuki coupling reaction. Eleven targeted compounds with over 50% inhibition against HL60 and A549 human cancer cell lines at 10 µM were further evaluated for the in vitro antitumor activities by MTT or SRB assay. The biological results revealed that some compounds exhibited potent antitumor activities. Thiophene derivative 6 and acetylphenyl derivative 5 were the most active ones against HL60 and A549 cell lines, with IC50 values less than 5 µM, which thus could be considered as useful candidate for further development of new antitumor agents.

Fasciospyrinadine, a novel sesquiterpene pyridine alkaloid from a Guangxi sponge Fasciospongia sp.

Fasciospyrinadine (1), a novel sesquiterpene pyridine alkaloid with a previously unreported skeleton featuring a monocyclicfarnesane moiety attached to a 3-methylenepyridine residue, was isolated from the sponge Fasciospongia sp. from Weizhou Island, Guangxi Autonomous Region. The structure and the relative stereochemistry of 1 were elucidated on the basis of extensive analysis of its 1D and 2D NMR spectroscopic techniques.