Ealamines A–H, a Series of Naphthylisoquinolines with the Rare 7,8′-Coupling Site, from the Congolese Liana Ancistrocladus ealaensis, Targeting Pancreatic Cancer Cells

Abstract

From the twigs and leaves of the Central African liana Ancistrocladus ealaensis (Ancistrocladaceae), a series of ten 7,8′-coupled naphthylisoquinoline alkaloids were isolated, comprising eight new compounds, named ealamines A−H (4a, 4b, 5−10), and two known ones, 6-O-demethylancistrobrevine A (11) and yaoundamine A (12), which had previously been found in related African Ancistrocladus species. Only one of the new compounds within this series, ealamine H (10), is a typical Ancistrocladaceae-type alkaloid, with 3S-configuration at C-3 and an oxygen function at C-6, whereas seven of the new alkaloids are the first 7,8′-linked "hybrid-type" naphthylisoquinoline alkaloids, i.e., 3R-configured and 6-oxygenated in the tetrahydroisoquinoline part. The discovery of such a broad series of 7,8′-coupled naphthyltetrahydroisoquinolines is unprecedented, because representatives of this subclass of alkaloids are normally found in Nature quite rarely. The stereostructures of the new ealamines were assigned by HRESIMS, 1D and 2D NMR, oxidative degradation, and experimental and quantum-chemical ECD investigations, andin the case of ealamine A (4a)also confirmed by X-ray diffraction analysis. Ealamines A−D exhibited distinctand specificantiplasmodial activities, and they displayed pronounced preferential cytotoxic effects toward PANC-1 human pancreatic cancer cells in nutrient-deprived medium, without causing toxicity under normal, nutrient-rich conditions, with ealamine C (5) as the most potent agent.N aphthylisoquinoline alkaloids 1−3 are the only di-and tetrahydroisoquinoline natural products that are not, as usual, built up from aromatic amino acids, 4 but from acetate/ malonate units, following a novel, polyketidic pathway to isoquinolines in plants. 5 Their two molecular halves, the naphthalene and the isoquinoline subunits, are formed separately, both from joint polyketide precursors, and are connected to each other at a quite late stage of the biosynthetic

Dimeric Pimprinine Alkaloids From Soil-Derived Streptomyces sp. NEAU-C99

“…To investigate the possible potential axial chirality in dimeric pimprinine molecules, CD spectra for dipimprinines A-D (1-4) were acquired (Figures S10, S18, S26, S34). Unlike the reported natural dimeric atropisomers (Wang et al, 2013;Tshitenge et al, 2019), no Cotton effects can be found in any CD spectra of dipimprinines A-D (1-4). Consequently, either dipimprinines A-D (1-4) have no atropisomeric stereochemistry (that's to say a plane structure) or they were all racemates.…”

The potential of anti-malarial compounds derived from African medicinal plants: a review of pharmacological evaluations from 2013 to 2019

“…The activities against the CQ-sensitive NF54 strain showed IC 50 values of 6.3, 4.9, 0.84 and 22.2 μM, respectively. Meanwhile, compounds 26, 27 and 29 inhibited the CQ-and pyrimethamine-resistant K1 strain with IC 50 values of 1.6, 1.4, and 8.2 μM, respectively [67].…”

“…Among the compounds identified from Ancistrocladaceae, Tshitenge et al also isolated four naphthylisoquinolines, named ealamines A-D (26 to 29, Fig. 8) from the twigs and leaves of Ancistrocladus ealaensis (Ancistrocladaceae) harvested in Mbandaka, DR Congo [67]. These compounds were tested against CQ-sensitive NF54 and CQ-and pyrimethamine-resistant K1 strains of P. falciparum.…”

Spirombandakamine A3 and Cyclombandakamines A8 and A9, Polycyclic Naphthylisoquinoline Dimers, with Antiprotozoal Activity, from a Congolese Ancistrocladus Plant

“…Ancistrocladus likoko , widely distributed in the North-Central region of the Congo Basin, produces 5,8′-coupled monomeric naphthylisoquinoline alkaloids exclusively, even in large quantities, along with a few 6′,6″-coupled dimeric analogues (referred to as michellamine-type dimers), which occur in very low concentrations. ,− The West-Central Congolese liana A. congolensis likewise contains 5,8′-linked monomeric naphthylisoquinoline alkaloids and michellamine-type dimers, but it additionally provides 5,1′- and 7,1′-coupled monomers. , A. ileboensis and A. ealaensis , by contrast, are much more “creative”, both at the monomeric and the dimeric level. The former one, endemic to the Southern Congo Basin, was shown to contain a number of 7,1′-, 5,1′-, 5,8′-, and 7,8′-connected monomers and several symmetric 3′,3″-coupled and the unsymmetric 3′,6′′-coupled dimers of 7,1′-linked monomers. ,, Ancistrocladus ealaensis from the North-Western region of the DRC was demonstrated to produce 5,8′-, 7,8′-, and N,C -coupled monomers and representatives of four subclasses of dimeric naphthylisoquinoline alkaloids: michellamine-type, korundamine-type (i.e., 6′,6″-coupled dimer with two different, 5,8′- and 7,8′-connectivities, at the outer axes), open-chain mbandakamine-type, and cyclombandakamine-type dimers. ,,− …”