Six New Dimeric Monoterpenoid Indole Alkaloids With Antiviral Activity From Gelsemium elegans

Six new dimeric monoterpenoid indole alkaloids, geleganidines D-I (1-6), together with six known analogues (7-12), were isolated from the roots of Gelsemium elegans. Compounds 1 and 2 represent the first dimeric Gelsemium alkaloids composed of a humantenine-type unit and a gelsedine-type unit, connected through a carbonyl-derived urea bridge. Compounds 3-6 were new dimeric monoterpenoid indole alkaloids featuring distinct dimerization patterns, including a carbonyl-derived urea bridge (3), azo linkages (4 and 5), and a symmetric C-C-linked dimer (6). Their structures and absolute configurations were elucidated by comprehensive spectroscopic analyses, including NMR, single-crystal X-ray diffraction, and quantum-chemical ECD calculations. Among the isolates, compounds 4, 5, and 8 exhibited significant in vitro anti-herpes simplex virus type 1 (HSV-1) activity, with IC₅₀ values of 5.01 ± 0.78, 12.55 ± 1.47, and 6.35 ± 0.36 µM, respectively. A preliminary structure-activity relationship analysis of compounds 1-12 was also discussed.