Organo NHC catalyzed aqueous synthesis of 4β-isoxazole-podophyllotoxins: anticancer, caspase activation, tubulin polymerization inhibition and molecular docking studies.

We present, for the first time, the organo--heterocyclic carbene (NHC) catalyzed 1,3-dipolar cycloaddition of 4β--propargyl podophyllotoxin (1) with aromatic nitrile oxides to afford regioselective 4β-isoxazolepodophyllotoxin hybrids (6a-n) in benign aqueous-organic media. Preliminary anticancer activity results showed that compound 6e displayed superior activity against MCF-7, HeLa and MIA PaCa2 human cell lines compared with podophyllotoxin. Compounds 6j and 6n showed greater activity against the MCF-7 cell line than the positive control.