Evaluation of synthetic coumarins for antiausterity cytotoxicity against pancreatic cancers

• Published in: Bioorganic & medicinal chemistry letters 2016-03, Vol.26 (5), p.1471-1474
• Main Authors: Farley, Conner M., Dibwe, Dya Fita, Ueda, Jun-ya, Hall, Eric A., Awale, Suresh, Magolan, Jakob
• Format: Article
• Language: English
• Subjects: Antiausterity agents; Antineoplastic Agents, Phytogenic - chemical synthesis; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Biological Products - chemical synthesis; Biological Products - chemistry; Biological Products - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Coumarins; Coumarins - chemical synthesis; Coumarins - chemistry; Coumarins - pharmacology; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Starvation-resistance; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2016.01.054

[Display omitted] 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.