Four new diterpenoid alkaloids from Aconitum japonicum subsp. subcuneatum

Abstract

Diterpenoid alkaloids with remarkable chemical properties and biological activities are frequently found in plants of the genera Aconitum, Delphinium, and Garrya. Accordingly, several diterpenoid alkaloid constituents of Aconitum and Delphinium plants as well as their derivatives exhibited cytotoxic activity against lung, prostate, nasopharyngeal, and vincristine-resistant nasopharyngeal cancer cell lines. Four new C-diterpenoid alkaloids, 14-anisoyllasianine (1), 14-anisoyl-N-deethylaconine (2), N-deethylaljesaconitine A (3), and N-deethylnevadensine (4), together with 17 known C- and C-diterpenoid alkaloids, were isolated in a phytochemical investigation of rhizoma of Aconitum japonicum THUNB. subsp. subcuneatum (NAKAI) KADOTA. Their structures were elucidated by extensive spectroscopic methods including NMR (1D and 2D), IR, and MS (HRMS). Eight known diterpenoid alkaloids, lipoaconitine, lipomesaconitine, aconine, nevadenine, talatisamine, nevadensine, ryosenamine, and dehydrolucidusculine, were isolated the first time from A. japonicum subsp. subcuneatum. Three of the new C-diterpenoid alkaloids (1, 3, 4) and six of the known diterpenoid alkaloids were evaluated for cytotoxic activity against five human tumor cell lines.

Cytotoxic Effects of Diterpenoid Alkaloids Against Human Cancer Cells

“…subsp. subcuneatum (NAKAI) KADOTA [22,23,24,25,26,27,28] (Figure 2). Two synthetic aconitine-type C 19 -diterpenoid alkaloids, 3,15-diacetyljesaconitine ( 7 ) [26] and 3-acetylmesaconitine ( 11 ) [29] prepared from secojesaconitine ( 6 ) and mesaconitine ( 8 ), respectively (Figure 2), were also tested.…”

“…Eighteen of the 23 tested aconitine-type C 19 -diterpenoid alkaloids, both natural alkaloids ( 1 ~ 6 , 8 ~ 10 , 12 ~ 14 , 18 ~ 23 ) and synthetic analogs ( 7 and 11 ), were inactive (IC 50 > 20 or 40 μM) [27,28,30] (Table 1). Three natural diterpenoid alkaloids ( 15 ~ 17 ) exhibited cytotoxic activity against five human tumor cell lines (A549, MDA-MB-231, MCF-7, KB, and MDR KB subline KB-VIN) (Table 1).…”

“…Lipojesaconitine ( 17 ) showed significant cytotoxicity against four tested cell lines with IC 50 values of 6.0 to 7.3 μM, but weak cytotoxicity against KB-VIN (IC 50 = 18.6 μM) [28]. Lipomesaconitine ( 15 ) showed moderate cytotoxicity against the KB cell line (IC 50 = 9.9 μM), but weak cytotoxicity against the other four human tumor cell lines (IC 50 =17.2 ~ 21.5 μM) [27]. Lipoaconitine ( 16 ) was weakly cytotoxic (IC 50 = 13.7 ~ 20.3 μM) against all five human tumor cell lines [28].…”

“…The tested lycoctonine-type (7,8-diol) C 19 -diterpenoid alkaloid group included 12 natural alkaloids, namely nevadensine ( 24 ), N -deethylnevadensine ( 25 ), and virescenine ( 27 ), purified from rhizoma of Aconitum japonicum subsp. subcuneatum [27], and 18-methoxygadesine ( 26 ), delphinifoline ( 28 ), delcosine ( 34 ), 14-acetyldelcosine ( 34–43 ), and 14-acetylbrowniine ( 35 ), purified from root of Aconitum yesoense var. macroyesoense (NAKAI) TAMURA [31,32,33,34], and andersonidine ( 30 ), pacifiline ( 31 ), pacifinine ( 32 ), and pacifidine ( 33 ), purified from seeds of Delphinium elatum cv.…”

“…Tested hetisine-type (analogs of kobusine) C 20 -diterpenoid alkaloids included four natural alkaloids, ryosenamine ( 64 ), 9-hydroxynominine ( 65 ), and torokonine ( 66 ), isolated from rhizoma of Aconitum japonicum subsp. subcuneatum [27,28] (Figure 6) and kobusine ( 67 ), purified from roots of Aconitum yesoense var. macroyesoense [31] (Figure 6).…”