Improving Cancer Cytotoxicity of Mithramycin Analogues with Semi-Synthetic Derivatives

Chemistry

Villaran, Marielena

Jenkins, Kaitlin

Miller, Evan

Scott, Daniel (Mentor)

English

Mithramycin (MTM) is an antibiotic produced naturally by the bacterium Streptomyces argillaceous. With the use of genetically engineered M7W1 mutant strain, the bacteria produces three new MTM analogues: MTM SK, MTM SDK, MTM SA. MTM SK and MTM SDK are more effective anticancer agents, while MTM SA is much less effective. The difference between MTM SA and the other analogues is the presence of a carboxylic acid in a key location, which is also thought to be the cause for the decreased cytotoxicity. In order to improve its anticancer ability, small molecules were used to modify MTM SA and remove the carboxylic acid. Using cytotoxicity assays with non-small cell lung cancer cells, the new derivatives showed significant cytotoxicity improvement compared to both MTM SA and MTM SK/SDK. Current work is focused on scaling up the reactions to allow complete structural characterization with NMR and mass spectrometry.