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

Mufusama, Jean-Pierre; Feineis, Doris; Mudogo, Virima; Kaiser, Marcel; Brun, Reto; Bringmann, Gerhard

doi:10.1039/c9ra01784d

Cited by 12 publications

(11 citation statements)

References 49 publications

(207 reference statements)

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“…For other wavelengths, the ECD curves of 4a and 4b, however, showed different, not fully reversed shapes. In many cases, [1][2][3]21,27,31 the ECD spectra of atropo-diastereomers are virtually opposite of each other, because the chiroptical behavior is largely dominated by the stronger biaryl chromophore and, thus, by the axial configuration. On the other hand, since the two apparently atropisomeric naphthylisoquinoline alkaloids4a and 4bwere diastereomers and not enantiomers, the appearance of nonopposite, but divergent ECD spectra should not be totally excluded.…”

Section: Journal Of Natural Productsmentioning

confidence: 99%

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

et al. 2019

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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

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Section: Journal Of Natural Productsmentioning

confidence: 99%

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

et al. 2019

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“…Different from 6 , however, the isoquinoline unit of 7-A had no N -methyl group. This was readily recognized from the shielded signals of C-1 (δ C 49.1) and C-3 (δ C 44.8) in 7-A , which are typical of naphthylisoquinoline alkaloids with a trans -configured N -demethylated 1,3-dimethyltetrahydroisoquinoline. ,− …”

Section: Resultsmentioning

confidence: 96%

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

et al. 2021

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Spirombandakamine A3 (7) is only the third known naphthylisoquinoline dimer with a spiro-fused novel molecular framework and the first such representative to possess a relative trans-configuration at the two chiral centers in both tetrahydroisoquinoline subunits. It was found in the leaves of a botanically as yet unidentified Congolese Ancistrocladus plant, which is morphologically closely related to the Central African taxon Ancistrocladus ealaensis. Likewise isolated were the new cyclombandakamines A8 (8) and A9 (9), which belong to another most recently discovered type of unusual oxygen-bridged naphthylisoquinoline dimers and two previously described “open-chain” analogues, mbandakamines C (10) and D (11). The full absolute stereostructures of these compounds were assigned by combining spectroscopic, chemical, and chiroptical methods. Preliminary biomimetic investigations indicated that both spirombandakamine- and cyclombandakamine-type dimers result from the oxidation of their open-chain mbandakamine-type congeners. The new dimeric alkaloids 7–9 displayed potent growth-inhibitory activity against Plasmodium falciparum, the protozoal pathogen causing malaria, and moderate effects on Trypanosoma brucei rhodesiense, the parasite responsible for African sleeping sickness.

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“…The seriousness of the disease prompted several research groups to work on the development of new antileishmanial agents and the class of scaffolds explored includes various quinolines, [10–13] chalcones, [14,15] nitroimidazole, [16] triazolopyrimidine, [17] pyrazolopyrimidine, [18,19] aminopyrazole, [20] triazine, [21,22] quinazoline, [23] thymidine, [24] triterpenoids, [25] and quinazolinone [26] . The isolation and synthesis of a new class of biaryl naphthylisoquinoline alkaloid ancistroealaine A ( 1a ) from Ancistrocladus ealaensis and other alkaloids ( 1b , 1c ), and their antileishmanial activity has generated interest in the development of new antileishmanial agents [27–29] . The modified analog of 1a & 1b (C−C axis biaryls), 1d (N−C axis biaryls, biaryl isoquinolinium salt) has shown much better antileishmanial activity [30] .…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis of Biaryl Piperidine Derivatives and Their Evaluation as Potential Antileishmanial Agents against Leishmania donovani Strain Ag83

Rathnakar

Sinha

Prasad

et al. 2021

Chemistry & Biodiversity

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We have developed a new series of simple biaryl piperidine derivatives (11-19) based on biaryl naphthylisoquinoline alkaloid Ealamine-A. The target compounds were synthesized, analyzed by spectral data, and evaluated for antileishmanial activity against Leishmania donovani strain Ag83 by MTT assay. The compounds have shown the best to moderate antileishmanial activity. The 5'-fluoro-2'-methoxyphenyl derivative 14 and 3',5'-difluorophenyl derivative 16 have inhibited the promastigotes by 86 % and 85 % after 24 h and 92 % and 91 % after 48 h incubation, respectively, at 400 μM concentration. The % inhibition was lower with the lowering of the concentration and increased with the incubation time. Compounds 12, 15, and 18 have solubility issues and proved to be less active than the rest of the compounds. Molecular docking studies were performed on selective active compounds and the results indicate that these compounds may act by binding to the Leishmanolysin and the docking scores are in good correlation with the antileishmanial activity. These results provide an initial insight into the design of new therapeutics for neglected tropical diseases.

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

Abstract: The discovery of the two unsymmetrically coupled dimeric naphthylisoquinoline alkaloids, the mbandakamines B3 and B4, showing a high steric hindrance at the central biaryl axis and displaying pronounced antiplasmodial activities, is described.

Cited by 12 publications

References 49 publications

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

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

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

Design, Synthesis of Biaryl Piperidine Derivatives and Their Evaluation as Potential Antileishmanial Agents against Leishmania donovani Strain Ag83

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

Abstract: The discovery of the two unsymmetrically coupled dimeric naphthylisoquinoline alkaloids, the mbandakamines B3 and B4, showing a high steric hindrance at the central biaryl axis and displaying pronounced antiplasmodial activities, is described.

Cited by 12 publications

References 49 publications

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

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

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

Design, Synthesis of Biaryl Piperidine Derivatives and Their Evaluation as Potential Antileishmanial Agents against Leishmania donovani Strain Ag83

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

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