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.