A series of functionalized coumarins were synthesized and evaluated for their capacity to inhibit the resistance to starvation of pancreatic cancer cells. This form of cytotoxicity, termed 'antiausterity' activity, was evaluated using a preferential cytotoxicity assay that compared cell survival in nutrient poor and nutrient rich conditions. Six of the seventeen compounds showed weak antiausterity activity against PANC-1. Compound 34 was active against PANC-1, MIA PaCa-2, and Capan-1 cancer cell lines. All of the compounds tested were simplified structural analogs of previously reported natural product leads. Six of the compounds, including 34, contain functionalized triazoles as novel potential bioisosteres of the side chain of the natural product angelmarin. Overall, the analogs were found to have low antiausterity activity relative to the corresponding natural products.
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http://dx.doi.org/10.1016/j.bmcl.2016.01.054 | DOI Listing |
J Med Chem
August 2024
Natural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Molecules
April 2024
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita 565-0871, Osaka, Japan.
The fungal genus is a rich source of structurally diverse secondary metabolites with remarkable pharmaceutical properties. The chemical constituents and anticancer activities of the marine-derived fungus have never been investigated. In this study, a bioactivity-guided investigation led to the isolation of eleven compounds, including trichodermamide A (), trichodermamide B (), aspergillazine A (), DC1149B (), ergosterol peroxide (), cerebrosides D/C (), 5-hydroxy-2,3-dimethyl-7-methoxychromone (), nafuredin A (), and harzianumols E/F (/).
View Article and Find Full Text PDFBiol Pharm Bull
February 2024
School of Pharmacy, Iwate Medical University.
CsPT4 is an aromatic prenyltransferase that synthesizes cannabigerolic acid (CBGA), the key intermediate of cannabinoid biosynthesis in Cannabis sativa, from olivetolic acid (OA) and geranyl diphosphate (GPP). CsPT4 has a catalytic potential to produce a variety of CBGA analogs via regioselective C-prenylation of aromatic substrates having resorcylic acid skeletons including bibenzyl 2,4-dihydroxy-6-phenylethylbenzoic acid (DPA). In this study, we further investigated the substrate specificity of CsPT4 using phlorocaprophenone (PCP) and 2',4',6'-trihydroxydihydrochalcone (THDC), the isomers of OA and DPA, respectively, and demonstrated that CsPT4 catalyzed both C-prenylation and O-prenylation reactions on PCP and THDC that share acylphloroglucinol substructures.
View Article and Find Full Text PDFBiol Pharm Bull
October 2023
Natural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama.
Pancreatic cancer cells have an inherent tolerance to withstand nutrition starvation, allowing them to survive in hypovascular tumor microenvironments that lack of sufficient nutrients and oxygen. Developing anti-cancer agents that target this tolerance to nutritional starvation is a promising anti-austerity strategy for eradicating pancreatic cancer cells in their microenvironment. In this study, we employed a chemical biology approach using the Ugi reaction to rapidly synthesize new anti-austerity agents and evaluate their structure-activity relationships.
View Article and Find Full Text PDFChem Biodivers
September 2023
Natural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, Toyama, 930-0194, Japan.
Pancreatic cancer is a highly aggressive form of cancer with a poor prognosis, partly due to 'austerity', a phenomenon of tolerance to nutrient deprivation and survival in its hypovascular tumor microenvironment. Anti-austerity agents which preferentially diminish the survival of cancer cells under nutrition starvation is regarded as new generation anti-cancer agents. This study investigated the potential of Piper longum constituents as anti-austerity agents.
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