Antiprotozoal Spirombandakamines A₁ and A₂, Fused Naphthylisoquinoline Dimers from a Congolese Ancistrocladus Plant

Abstract

From the leaves of a yet undescribed Congolese Ancistrocladus species, two novel naphthylisoquinoline dimers, spirombandakamines A (1) and A (2), were isolated, together with a new, but "classical" dimer, mbandakamine B (3). The cage-like stereostructures of 1 and 2 were established by combining spectroscopic, chemical, and chiroptical methods with quantum-chemical ECD calculations. Their unique molecular frameworks may originate from "open-chain" dimers, such as 3, by an oxidation-induced cascade of reactions. They possess strong antiprotozoal properties.

Michellamines A6 and A7, and further mono- and dimeric naphthylisoquinoline alkaloids from a Congolese Ancistrocladus liana and their antiausterity activities against pancreatic cancer cells

“…Owing to the pronounced antiprotozoal activities of some naphthylisoquinoline alkaloids, 1,19,[21][22][23] the two new monomers ancistrobonsolines A 1 (5) and A 2 (6) were tested against the pathogens causing malaria (Plasmodium falciparum), human African sleeping sickness (Trypanosoma brucei rhodesiense), Chagas' disease (T. cruzi), and visceral leishmaniosis (Leishmania donovani). The other isolated new dimeric metabolites were not evaluated, since their analogs had previously been found inactive.…”

Antiprotozoal dimeric naphthylisoquinolines, mbandakamines B3 and B4, and related 5,8′-coupled monomeric alkaloids, ikelacongolines A–D, from a Congolese Ancistrocladus liana

“…[1][2][3] Comprehensive data about the natural diversity of the genus Ancistrocladus within the Congo region, however, are still lacking. 1,3 Recent eld trips in combination with phylogenetic and phytochemical investigations clearly suggested the presence of further, hitherto unrecognized taxa, [3][4][5][6][7][8][9][10][11] along with the four botanically acknowledged Ancistrocladus species, 1,2,12,13 A. congolensis J. Léonard, A. likoko J. Léonard, A. ealaensis J. Léonard, and A. ileboensis Heubl, Mudogo & G. Bringmann. The latter species was discovered in the Southern Congo Basin, and described for the rst time in 2010, 12 whereas the three other Congolese taxa were botanically acknowledged for the rst time in 1949.…”

“…It is all the more remarkable that phytochemical investigations on Central African Ancistrocladus plants have picked up speed only quite recently, during the past decade, [4][5][6][7][8][9][10][11][14][15][16][17][18][19][20][21] considering that intense isolation work on Asian as well as West and East African taxa had started much earlier, leading to the discovery of structurally unique mono-and dimeric naphthylisoquinoline alkaloids with promising antiparasitic and antiviral activities. [22][23][24][25][26][27] More recent phytochemical studies on Ancistrocladus lianas from the Congo region, including all of the four valid taxa [14][15][16][17][18][19][20][21] mentioned above, but also botanically as yet unidentied plants, [4][5][6][7][8][9][10][11] furnished a whole series of further novel-type naphthylisoquinoline alkaloids, among them N,Ccoupled compounds 9,10 and, in particular, dimeric representatives with complex molecular architectures. [4][5][6]…”

“…[22][23][24][25][26][27] More recent phytochemical studies on Ancistrocladus lianas from the Congo region, including all of the four valid taxa [14][15][16][17][18][19][20][21] mentioned above, but also botanically as yet unidentied plants, [4][5][6][7][8][9][10][11] furnished a whole series of further novel-type naphthylisoquinoline alkaloids, among them N,Ccoupled compounds 9,10 and, in particular, dimeric representatives with complex molecular architectures. [4][5][6][7][8][14][15][16]18,21 Some of these secondary metabolites attracted attention due to their extraordinary antiplasmodial 6,8,15,16 or antileishmanial 10 activities or, according to their individual structures, to their strong antiproliferative effects against human leukemia, 16,18,20 cervical HeLa, 7,21 or pancreatic cancer cells. 7,9,…”

“…The central axis of 1 and 2 is thus located in one of the peri-positions of the 'northwestern' naphthalene portion, neighboring one of the outer axes in the adjacent peri-position, which gives rise to a rotationally strongly hindered central binaphthalene linkage. 4,6,16 With the two outer axes being chiral, too, 1 and 2 possess three consecutive stereogenic axes, and, thus, together with four stereogenic centers in their two tetrahydroisoquinoline subunits, a total of seven elements of chirality. 4,6,16 The two mbandakamines exerted promising antiplasmodial and antitrypanosomal activities in vitro, 4,6 and mbandakamine A (1) was also found to display strong cytotoxic activities against drug-sensitive (CCRF-CEM) and multidrug-resistant (CEM/ADR5000) human leukemia cells.…”