Jozilebomines A and B, Naphthylisoquinoline Dimers from the Congolese Liana Ancistrocladus ileboensis, with Antiausterity Activities against the PANC-1 Human Pancreatic Cancer Cell Line

Abstract

Two new naphthylisoquinoline dimers, jozilebomines A (1a) and B (1b), were isolated from the roots of the Congolese plant Ancistrocladus ileboensis, along with the known dimer jozimine A (2). These compounds are Dioncophyllaceae-type metabolites, i.e., lacking oxygen functions at C-6 and with an R-configuration at C-3 in their tetrahydroisoquinoline moieties. The dimers 1a and 1b consist of two 7,1'-coupled naphthylisoquinoline monomers linked through an unprecedented 3',6″-coupling in the binaphthalene core and not, as in 2, via the C-3-positions of the two naphthalene units. Thus, different from the C-symmetric jozimine A (2), the new jozilebomines are constitutionally unsymmetric. The central biaryl axis of each of the three dimers is rotationally hindered, so that 1a, 1b, and 2 possess three consecutive chiral axes. The two jozilebomines have identical constitutions and the same absolute configurations at all four stereogenic centers, but differ from each other in their axial chirality. Their structural elucidation was achieved by HRESIMS, 1D and 2D NMR, oxidative degradation, and experimental and calculated ECD data. They exhibited distinct and specific antiplasmodial activities. All dimers showed potent cytotoxicity against HeLa human cervical cancer cells and preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition-deprived conditions. Furthermore, these dimers significantly inhibited the colony formation of PANC-1 cells, even when exposed to noncytotoxic concentration for a short time. Jozilebomines A (1a) and B (1b) and jozimine A (2) represent novel potential candidates for future drug development against pancreatic cancer.

Unraveling Plant Natural Chemical Diversity for Drug Discovery Purposes

“…In the data gathered in Table 4, as previously commented, it can be observed that even in the same plant species and same organ, different compounds have been characterized like jozilebomines and dioncophyllines in Ancistrocladus ileboensis leaves (J. Li et al, 2017d;J. Li et al, 2017c) or xanthohumol and a-acid derivatives such as humulones in Humulus lupulus flowers (J.…”

Biomimetic Total Synthesis of Mbandakamine A and Further Antiplasmodial Naphthylisoquinoline Dimers

“…In view of the promising anti‐infective activities of some dimeric naphthylisoquinolines,,, the new products were tested against the protozoan parasites causing malaria, African sleeping sickness, and leishmaniasis. Most remarkable was the excellent antiplasmodial activity of 17 against the chloroquine‐resistant K1 strain of Plasmodium falciparum in vitro (IC 50 =0.003 μ M), combined with a very low cytotoxicity (IC 50 =62.26 μ M), making a selectivity index of more than 20,000 – better than any mono‐ or dimeric naphthylisoquinolines ever tested ,…”

“…They consist of a naphthalene and an isoquinoline portion, both derived from polyketide precursors,, linked together by a biaryl axis that is, in most cases, rotationally hindered and, thus, stereogenic. Depending on their individual structures, they have pronounced anti‐infective or antitumoral activities ,. More than 200 representatives of this unique class of natural products have so far been isolated, among them more than 20 dimers, which possess even three biaryl axes ,.…”

“…Depending on their individual structures, they have pronounced anti‐infective or antitumoral activities ,. More than 200 representatives of this unique class of natural products have so far been isolated, among them more than 20 dimers, which possess even three biaryl axes ,. A structurally most fascinating dimer is mbandakamine A ( 1 a ) (see Figure ), which has recently been isolated, along with its M ‐configured atropo‐diastereomer mbandakamine B ( 1 b ), from the leaves of a botanically as yet undescribed Ancistrocladus species growing in the proximity of the town of Mbandaka in the Democratic Republic of the Congo .…”

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

“…24 In brief, exponentially growing cells were harvested and plated in 96-well plates (2 Â 10 3 per well) in DMEM and allowed to attach for 24 h in the humidied CO 2 incubator at 37 C. The cells were then washed with phosphate-buffered saline (PBS) followed by the addition of serially diluted test samples in DMEM. For each concentration, three replications were performed.…”