10-N-heterocylic aryl-isoxazole-amides (AIMs) have robust anti-tumor activity against breast and brain cancer cell lines and useful fluorescence properties

A series of 10-N-heterocyclic anthracenyl isoxazole amides (N-Het-AIMs) were prepared by Suzuki palladation followed by lanthanide double activation. The compounds showed robust antitumor activity against both breast and brain tumor cells lines. NMR and CD melting indicate interaction with the c-myc oncogene, the working hypothesis, and a molecular dynamics study provided a basis for rationalizing the possible drug-receptor interaction. The N-Het-AIMs have significant fluorescence and could be applied as useful theranostic agents. [Display omitted] A novel series of anthracenyl-isoxazole amide (AIM) antitumor agents containing N-heterocycles in the 10 position (N-het) were synthesized using palladium cross-coupling. The unique steric environment of the N-het-AIMs required individual optimization in each case. Lanthanide mediated double activation was used to couple the dimethylamino pyrrole moiety, required for antitumor action. Robust antitumor activity was observed against breast and brain cancer cell lines. The compounds were docked with the c-myc oncogene promoter sequence, which adopts a G4 quadruplex DNA conformation, and represents the working hypothesis for biological action. The N-het-AIMs have useful fluorescence properties, allowing for observation of their distribution within tumor cells.