Antiviral Limonoids Including Khayanolides from the Trang Mangrove Plant <i>Xylocarpus moluccensis</i>

Eight new khayanolides, named thaixylomolins G–N (<b>1</b>–<b>8</b>), two new phragmalins (<b>9</b> and <b>10</b>), and two new mexicanolides (<b>11</b> and <b>12</b>) were obtained from the seeds of the Trang mangrove plant <i>Xylocarpus moluccensis</i>. The absolute configurations of these limonoids, except for the stereocenter at C-6 of <b>11</b> and <b>12</b>, were assigned by experimental and TDDFT calculated electronic circular dichroism spectra. The khayanolides may be classified into two subclasses, one of which has a C-2 carbonyl and a 3β-acetoxy group, whereas the other possesses a 2β-acetoxy and a C-3 carbonyl function. Khayanolides, rearranged phragmalin-type limonoids, are reported for the first time from plants of the mangrove genus <i>Xylocarpus</i>. The structure of moluccensin J, a known 30-ketophragmalin containing a Δ⁸⁽¹⁴⁾ double bond, was revised to be a khayanolide, named thaixylomolin K. The antiviral activities of the isolates against pandemic influenza A virus (subtype H1N1) were tested by the assay of cytopathic effect inhibition. Three khayanolides, viz., thaixylomolins I, K, and M, exhibited moderate anti-H1N1 activities. The most potent one, thaixylomolin I (IC₅₀ = 77.1 ± 8.7 μM), showed stronger inhibitory activity than that of the positive control, ribavirin (IC₅₀ = 185.9 ± 16.8 μM)