Fifteen new isocoumarin derivatives 1-3, (±)-4, (±)-5, 6-10, (+)-11, (+)-12, and 13, together with eleven known analogues (-)-11, (-)-12, and 14-22 were isolated from the mangrove endophytic fungus Alternaria sp. HN-17. Their structures were unambiguously established by 1D/2D NMR and HRESIMS spectra, and electronic circular dichroism (ECD) calculations. Alterisocoumarin A (1) possesses a rare 6/6/6/5 tetracyclic skeleton featuring a γ-butyrolactone-fused dibenzo-α-pyrone core, while 2 and 3 have an unusual chlorinated furan ring system. In bioassay, compounds 1, (-)-4, 10, and 18 displayed good anti-inflammatory activity with IC50 values ranging from 10.68 to 28.05 μM than positive control (L-NMMA: 32.83 μM). Moreover, 1 exerts anti-inflammatory effects by down-regulated expression the NF-κB and MAPK pathways. In addition, compounds 21 and 22 showed notable anti-tuberculosis activities by inhibiting MptpA, MptpB and PTP1B. The molecular docking results showed that compound 22 binds deeply in the active cavity of PTP1B.
