noscapine and Pancreatic-Neoplasms

The macrocyclic diarylether heptanoid (MDEH) natural products have been used in folk medicine for centuries. MDEHs are reported to exert anti-tumor properties by inhibiting the activation of NF-κB. Here we report the synthesis of a small MDEH library (first reported synthesis of racemic platycarynol) using a Grubbs cross metathesis/Ullmann cyclization strategy. Evaluation of the library led to the identification of MDEH 9b which sensitizes pancreatic cancer cells to gemcitabine mediated growth inhibition and apoptosis.

Topics: Antineoplastic Agents; Apoptosis; Biological Products; Cell Line; Chemistry, Pharmaceutical; Drug Design; Ether; HEK293 Cells; Humans; Models, Chemical; NF-kappa B; Pancreatic Neoplasms; Time Factors; Tumor Necrosis Factor-alpha