Discovery of Cyclic Diarylheptanoids as Inhibitors against Influenza A Virus from the Roots of Casuarina equisetifolia

Four new cyclic diarylheptanoids, casuarinols A-C (1-3) and casuarinolide A (4), together with six known ones (5- 10), were isolated from the roots of Casuarina equisetifolia. Structures were elucidated by extensive spectroscopic analysis, theoretical conformational, and electronic circular dichroism analyses. Casuarinol C (3) is a novel cyclic diarylheptanoid-aldehyde adduct. Casuarinolide A (4) represents the first structure of a seco-cyclic diarylheptanoid. Compounds 1-9 were evaluated for their anti influenza A virus (IAV) activity against A/WSN/33 (H1N1). (-)-(M)-11-Oxo-3,12R,17-trihydroxy-9-ene-[7,0]-metacyclophane (5) displayed significant anti-IAV activity with an IC50 value of 8.64 +/- 2.49 mu M and a CC50 higher than 100 mu M.