Sarniensine, a mesembrine-type alkaloid isolated from Nerine sarniensis, an indigenous South African Amaryllidaceae, with larvicidal and adulticidal activities against Aedes aegypti

Abstract

A new mesembrine-type alkaloid, named sarniensine, was isolated together with tazettine, lycorine, the main alkaloid, and 3-epimacronine from Nerine sarniensis, with the last two produced for the first time by this plant. This Amaryllidaceae, which is indigenous of South Africa, was investigated for its alkaloid content, because the organic extract of its bulbs showed strong larvicidal activity with an LC value of 0.008μgμL against first instar Aedes aegypti larvae and with an LD value 4.6μg/mosquito against adult female Ae. aegypti, which is the major vector for dengue, yellow fever and the Zika virus. The extract did not show repellency at MED value of 0.375mgcm against adult Ae. aegypti. Sarniensine was characterized using spectroscopic and chiroptical methods as (3aR,4Z,6S,7aS)-6-methoxy-3a-(2'-methoxymethyl-benzo [1,3]dioxol-1'-yl)-1-methyl-2,3,3a,6,7,7a-hexahydro-1H-indole. It was less effective against larva at the lowest concentration of 0.1μgμL, however it showed strong adulticidal activity with an LD value of 1.38±0.056μgmosquito.

Amaryllidaceae alkaloids: Absolute configuration and biological activity

“…Thus, the absolute configuration R , Z , S, and S were assigned to C‐3a, the double bond between C‐4 and C‐5, C‐6, and C‐7a. Furthermore, the correlations observed in the NOESY spectrum between CH 2 OMe and H‐2B, H‐3B, H‐4 and H‐7a and between H‐7a and CH 2 OMe and H‐6′, proved that the A/B ring system was bent over the 1,3‐dioxol‐tetrasubstituted benzene ring …”

“…The absolute configuration of 3a S ,4 Z ,6 S ,7a S was assigned to sarniensinol ( 46 ) by comparing its ECD spectrum with that of sarniensine, as well as with spectra reported in the literature for egonine and tazettadiol isolated from H. equestre . A notable discovery was that the alkaloids sarniensinol ( 46 ), sarniensine ( 47 ), egonine ( 48 ), and tazettadiol all displayed similar profiles in the CD spectra in the region between 225 and 260 nm, while sarniensinol ( 46 ) displayed an opposite Cotton effect with respect to the other three alkaloids at about 290 nm.…”

“…This observation suggests that the A/B ring fusion for 46 is trans and opposite to that of egonine, tazettadiol, and sarniensine, which are all cis . This opposite stereochemistry is probably the main reason for the significant different value for the coupling constant measured between the two olefinic protons H‐4 and H‐5 in ring A appearing as broad singlets compared to the same protons observed as doublets in 47 and 48 …”

“…32 , 46 , and 47 were characterized by extensive spectroscopic investigation. Their relative configurations were assigned by 1 H and NOESY NMR spectra . The 1 S ,2 S ,4a R ,10b S absolute configurations of 32 and the similar bowdensine ( 33 ) were assigned by comparing their ECD spectra with those reported in literature for the similar crinine alkaloids .…”

“…As for the structure–activity relationship, the pretazettine scaffold in 46 and 47 and the crinine one in crinsarnine and 33 proved to be important for their activity as the pyrrole[ de ]phenathridine scaffold was for the activity of hippadine and 1‐ O ‐acetyllycorine. Among the pretazettine group, 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 (Table ) …”