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
Date
2016-10-27
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Abstract
Two new Amaryllidaceae alkaloids, belonging to the mesembrine- and crinine-types,
named crinsarnine (1) and sarniensinol (2), were isolated from the dried bulbs of Nerine sarniensis
together with bowdensine (3), sarniensine (4), hippadine (5) and 1-O-acetyl-lycorine (6). Crinsarnine
(1) and sarniensinol (2) were characterized using spectroscopic and chiroptical methods as
(1S,2S,4aR,10bS)-2,7-dimethoxy-1,2,3,4,4a,6-hexahydro-5,11b-ethano[1,3]dioxolo-[4,5-j]phenanthridin-
1-yl acetate and (6-(3aR,4Z,6S,7aS)-6-methoxy-1-methyl-2,3,3a,6,7,7a-hexa-hydro-1H-indol-3a-yl)benzo
[d][1,3]dioxol-5-yl)methanol, respectively. Furthermore, the complete spectroscopic characterization
of bowdensine (3) is reported for the first time. Compounds 1–6 were evaluated against the
Orlando reference strain of Aedes aegypti. None of compounds showed mortality against 1st instar
Ae. aegypti larvae at the concentrations tested. In adult topical bioassays, only 1 displayed adulticidal
activity with an LD50 = 2.29 ± 0.049 µg/mosquito. As regards the structure-activity relationship,
the pretazettine and crinine scaffold in 2 and 4 and in 1 and 3 respectively, proved to be important
for their activity, while the pyrrole[de]phenanthridine scaffold present in 5 and 6 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 trans-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
Description
CITATION: Masi, M. et al. 2016. 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. Molecules, 21(11):1432, doi:10.3390/molecules21111432.
The original publication is available at http://www.mdpi.com/journal/molecules
The original publication is available at http://www.mdpi.com/journal/molecules
Keywords
Nerine sarniensis, Aedes aegypti, Zika virus, Amaryllidaceae, Alkaloids
Citation
Masi, M. et al. 2016. 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. Molecules, 21(11):1432, doi:10.3390/molecules21111432.