Synthesis of neolignans as microtubule stabilisers

Tubulin is a well established target for anticancer drug development. Lignans and neolignans were synthesized as tubulin interacting agents. Neolignans 10 and 19 exhibited significant anticancer activity against MCF-7 and MDAMB-231 human breast cancer cell lines. Both the compounds effectively induced stabilization of microtubule at 4 and 20 μM concentrations respectively. Neolignan 10 induced G2/M phase arrest in MCF-7 cells. Docking experiments raveled that 10 and 19 occupied the same binding pocket of paclitaxel with some difference in active site amino acids and good bioavailability of both the compounds. In in vivo acute oral toxicity 10 was well tolerated up to 300 mg/kg dose in Swiss-albino mice.

Lignans and neolignans were synthesized as tubulin interacting agents. Neolignan 10, the best candidate of the series showed microtubulin stabilization, induced apoptosis by G2/M phase arrest and was found to be non-toxic up to 300 mg/kg dose in Swiss albino mice in acute oral activity.Figure optionsDownload as PowerPoint slide