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

Authors: MASI, MARCO - University Of Naples; CALA, ANTONIO - University Of Naples; Tabanca, Nurhayat; CIMMINO, ALESSIO - University Of Naples; GREEN, IVAN - University Of Stellenbosch; BLOOMQUIST, JEFFREY - University Of Florida; VAN OTTERLO, WILLEM - University Of Stellenbosch; MACIAS, FRANCISCO - University Of Cadiz; EVIDENTE, ANTONIO - University Of Naples

Submitted to: Molecules
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/19/2016
Publication Date: 10/27/2016
Citation: Masi, M., Cala, A., Tabanca, N., Cimmino, A., Green, I.R., Bloomquist, J.R., Van Otterlo, W.A., Macias, F.A., Evidente, A. 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. 2016: 21(11), 1432. https://doi.org/10.3390/molecules21111432.
DOI: https://doi.org/10.3390/molecules21111432

Interpretive Summary: Natural products are considered more environmentally friendly for pest management. A scientist from the USDA-ARS (Miami, FL), in collaboration with chemists at the University of Naples (Napoli, Italy), University of Stellenbosch (Stellenbosch, South Africa), University of Cádiz (Cádiz, Spain) and a toxicologist from University of Florida (Gainesville, Florida) conducted a study to investigate new products to control and kill mosquitoes that spread disease. Chemical study of the South African plant called Nerine sarniensis has identified two new alkaloids in addition to 4 known alkaloids. Primary bioassays found that the compounds were not active against Aedes aegypti first instar larvae but had better adulticidal activity, therefore, the isolated compounds were only tested against adult mosquitoes. One compound (crinsarnine) was highly active against Aedes aegypti adults and additional studies are required to determine activity against other mosquito species. Results from the current study indicate that structure-activity investigations with respect to the mosquitocidal activity of compounds belonging to pretazettine and crinine carbon skeleton are warranted. This could lead to new compounds with improved insecticidal activity.

Technical 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 the 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 ug/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.