Alkaloids with Activity Against the Zika Virus Vector Aedes Aegypti (L.)-Crinsarnine and Sarniensinol, Two New Crinine and Mesembrine Type Alkaloids Isolated from the South African Plant Nerine Sarniensis

Two new Amaryllidaceae alkaloids, belonging to the mesembrine- and crinine-types, named crinsarnine () and sarniensinol (), were isolated from the dried bulbs of together with bowdensine (), sarniensine (), hippadine () and 1--acetyl-lycorine (). Crinsarnine () and sarniensinol () were characterized using spectroscopic and chiroptical methods as (1,2,4a,10b)-2,7-dimethoxy-1,2,3,4,4a,6-hexahydro-5,11b-ethano[1,3]dioxolo-[4,5-]phenanthridin-1-yl acetate and (6-(3a,4,6,7a)-6-methoxy-1-methyl-2,3,3a,6,7,7a-hexa-hydro-1-indol-3a-yl)benzo[][1,3]dioxol-5-yl)methanol, respectively. Furthermore, the complete spectroscopic characterization of bowdensine () is reported for the first time. Compounds - were evaluated against the Orlando reference strain of . None of compounds showed mortality against 1st instar larvae at the concentrations tested. In adult topical bioassays, only displayed adulticidal activity with an LD = 2.29 ± 0.049 μg/mosquito. As regards the structure-activity relationship, the pretazettine and crinine scaffold in and and in and respectively, proved to be important for their activity, while the pyrrole[]phenanthridine scaffold present in and was important for their reactivity. Among the pretazettine group compounds, opening of the B ring or the presence of a B ring lactone as well as the -stereochemistry of the A/B ring junction, appears to be important for activity, while in crinine-type alkaloids, the substituent at C-2 seems to play a role in their activity.