A Near-Complete Series of Four Atropisomeric Jozimine A₂-Type Naphthylisoquinoline Dimers with Antiplasmodial and Cytotoxic Activities and Related Alkaloids from Ancistrocladus abbreviatus

Abstract

Three new naphthylisoquinoline dimers, jozibrevines A–C (1a–c), were isolated from the West African shrub Ancistrocladus abbreviatus, along with the known dimer jozimine A2 (1d). The two molecular moieties of 1a–d are coupled via the sterically constrained 3′,3″-positions of their two naphthalene units, so that the central biaryl linkage is rotationally hindered. With the two outer axes also being chiral, 1a–d possess three consecutive stereogenic axes. The four isolated dimers all have the same constitutions and identical absolute configurations at the four stereogenic centers, but differ by their axial chirality. They belong to the extremely small class of Dioncophyllaceae-type naphthyl­isoquinoline dimers, i.e., being devoid of oxygen functions at C-6 and bearing the R-configuration at C-3 in their isoquinoline portions. Besides these dimers, the plant produces predominantly typical Ancistrocladaceae-type monomeric compounds, i.e., with the S-configuration at C-3 and an oxygen function at C-6, such as the new ancistrobrevines K (5) and L (6). Furthermore, a new hybrid-type (i.e., mixed Ancistrocladaceae/Dioncophyllaceae-type) alkaloid was identified, named ancistrobrevine M (7), which is 3R-configured and 6-oxygenated. Remarkable was the discovery of its “inverse hybrid-type” counterpart, dioncoline A (8). It is the as yet only known 3S-configured naphthylisoquinoline lacking an O-functionality at C-6. The new jozibrevines A–C (1a–c) exhibited pronounced antiplasmodial activities in the submicromolar range, with 1a being the most potent compound (IC50, 0.012 μM). Furthermore, jozimine A2 (1d) showed cytotoxicity against human colon carcinoma (HT-29), fibrosarcoma (HT1080), and multiple myeloma (MM.1S) cancer cells, displaying IC50 values of 12.0, 9.0, and 5.0 μM, respectively, whereas jozibrevines A (1a) and B (1b) were nontoxic in this concentration range.

Multiple Myeloma Inhibitory Activity of Plant Natural Products

“…Another dimeric alkaloid, the naphtylisoquinoline dimer jozimine A2 was isolated from Ancistrocladus abbreviatus and tested for its effect on MM1S and two other cancer cell lines using an MTT assay [ 26 ]. The IC 50 value for MM1S was determined with 5.0 µM after 24 h of incubation.…”

pysisyphus: Exploring potential energy surfaces in ground and excited states

“…The biaryl motif plays a key role in many pharmaceutical compounds, [140] such as antihypertensive sartans [141] and nonsteroidal antiinflammatory drugs, [142,143] and also in natural products [144] such as cannabinol [145] and many alkaloids. [146][147][148] Selective cross-coupling of aryl-residues is often achieved by using transition metal catalysts. [149][150][151][152][153][154][155][156] As transition metal catalysts are often toxic and expensive, metal-free aryl cross-coupling reactions have also been proposed.…”

New Isoquinoline Alkaloids from Paraphaeosphaeria sporulosa F03, a Fungal Endophyte Isolated from Paepalanthus planifolius

“…Isoquinoline alkaloids (IQAs) are a large class of secondary metabolites produced not only by plants, but also by animals and microorganisms. They have been shown to possess a broad array of bioactivities, including antiplasmodial [4], antibacterial [5], and antifungal properties [6], enzyme inhibitory activities [7], and cytotoxicity against tumor cell lines [8]. IQAs also play an important role in the defense of plants against pathogens and herbivore attack [9].…”