Tanzawaic acid derivatives from a marine isolate of Penicillium sp. (SF-6013) with anti-inflammatory and PTP1B inhibitory activities.

Chemical investigation of a marine-derived fungus Penicillium sp. SF-6013 resulted in the discovery of a new tanzawaic acid derivative, 2 E ,4 Z -tanzawaic acid D ( 1 ), together with four known analogues, tanzawaic acids A ( 2 ) and D ( 3 ), a salt form of tanzawaic acid E ( 4 ), and tanzawaic acid B ( 5 ). Their structures were mainly determined by analysis of NMR and MS data, along with chemical methods. Preliminary screening for anti-inflammatory effects in lipopolysaccharide (LPS)-activated microglial BV-2 cells showed that compounds 1 , 2 , and 5 inhibited the production of nitric oxide (NO) with IC 50 values of 37.8, 7.1, and 42.5 μM, respectively. Compound 2 also inhibited NO production in LPS-stimulated RAW264.7 murine macrophages with an IC 50 value of 27.0 μM. Moreover, these inhibitory effects correlated with the suppressive effect of compound 2 on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated RAW264.7 and BV2 cells. In addition, compounds 2 and 5 significantly inhibited the activity of protein tyrosine phosphatase 1B (PTP1B) with the same IC 50 value (8.2 μM). [ABSTRACT FROM AUTHOR]