Structure Based Design of Tubulin Binding 9-Arylimino Noscapinoids: Chemical Synthesis and Experimental Validation Against Breast Cancer Cell Lines

A novel class of noscapine derivatives known as 9-arylimino noscapinoids was designed by substituting arylimino groups (Schiff bases) at the C-9 position. These molecules were docked with αβ-tubulin complex and a panel three top scoring molecules, 4-6 based on docking score screened out. bind tubulin robust predicted binding energy -37.24 kcal/mol -45.41 for 4, -39.73 -47.74 5, -43.62 -49.72 6 respectively compared to (-34.47 -40.27 kcal/mol) using molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) mechanics/generalized Born (MM/GBSA). chemically synthesized demonstrated experimentally high affinity noscapine. The anti-proliferative activity revealed inhibitory concentration (IC50 value) in between 3.6 32.6 µM MCF-7 MDA-MB-231 human breast cancer cell lines group primary tumor cells. All shown inhibit mitotic progression G2/M phase induce apoptosis cells different level. Thus, we conclude that have tremendous potential chemotherapeutic agents treatment cancer.