article · RSC Advances
Researchers have isolated several new and known naphthylisoquinoline alkaloids from the leaves of an unidentified Congolese Ancistrocladus liana. The newly identified compounds include dimeric alkaloids named michellamines A6, A7, B4, and B5, alongside monomeric alkaloids named ancistrobonsolines A1 and A2. Five previously reported compounds were also identified from the extracts. Structural analysis indicated distinct chemical profiles that differentiate this plant from related species, suggesting it may represent a new botanical taxon. Laboratory evaluations revealed that ancistrobonsolines A1 and A2 displayed strong, preferential cytotoxicity against human PANC-1 pancreatic cancer cells under nutrient-deprived conditions, while displaying no toxicity in nutrient-rich conditions. In addition, michellamines A6 and E demonstrated cytotoxic activity against cervical HeLa cancer cells that was comparable to the standard chemotherapy agent 5-fluorouracil. Ancistrobonsolines A1 and A2 also exhibited weak-to-moderate antiprotozoal activity.
Pancreatic tumours often thrive in nutrient-poor microenvironments, making antiausterity agents valuable starting points for therapeutic research. Discovering natural molecules that kill cancer cells under starvation without harming them under normal conditions could inform the design of targeted, less toxic therapies. Additionally, uncovering potent compounds from unclassified tropical plants highlights the role of botanical biodiversity in providing novel chemical scaffolds for oncology and infectious disease research.
This research provides early-stage lead compounds for pharmaceutical developers and oncology researchers seeking selective treatments for pancreatic and cervical cancers. The antiausterity mechanism observed in pancreatic cells presents an avenue for targeted drug design. However, as the work is strictly at the stage of early laboratory screening and cell-based assays, significant preclinical development, synthetic scaling, and animal testing are required before any real-world clinical application could be pursued.
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Michellamines A<sub>6</sub> (1) and A<sub>7</sub> (2) are the first dimers of 5,8'-coupled naphthylisoquinoline alkaloids with <i>cis</i>-configured stereocenters in both tetrahydroisoquinoline subunits. They were isolated from the leaves of a recently discovered, yet unidentified Congolese <i>Ancistrocladus</i> liana that shares some morphological characteristics with <i>Ancistrocladus likoko</i>. Two further new dimeric analogs, michellamines B<sub>4</sub> (3) and B<sub>5</sub> (4), were obtained, along with two previously likewise unknown monomers, ancistrobonsolines A<sub>1</sub> (5) and A<sub>2</sub> (6), which, besides one single known other example, are the only naphthyldihydroisoquinolines with an <i>M</i>-configured biaryl axis and <i>R</i>-configuration at C-3. Moreover, five compounds earlier reported from other <i>Ancistrocladus</i> species were identified, ancistroealaine C (7), korupensamines A (8a) and B (8b), and michellamines A<sub>2</sub> (9) and E (10). Their complete structural elucidation succeeded due to the fruitful interplay of spectroscopic, chemical, and chiroptical methods. Chemotaxonomically, the stereostructures of the metabolites clearly delineate this Congolese <i>Ancistrocladus</i> liana from all known related species, showing that it might be a new taxon. Ancistrobonsolines A<sub>1</sub> (5) and A<sub>2</sub> (6) exhibited strong preferential cytotoxicities against human PANC-1 pancreatic cancer cells under nutrient-deprived conditions, without displaying toxicity in normal, nutrient-rich medium. Against cervical HeLa cancer cells, the dimeric alkaloids michellamines A<sub>6</sub> (1) and E (10) displayed the highest cytotoxic activities, comparable to that of the standard agent, 5-fluorouracil. Furthermore, ancistrobonsolines A<sub>1</sub> (5) and A<sub>2</sub> (6) showed weak-to-moderate antiprotozoal activities.
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DOI: 10.1039/c8ra00363g
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