LAUSR

ABSTRACT A novel library of C2‐substituted tryptamines (based on diverse C2‐aroyl/arylimino indoles and indole‐diketopiperazine hybrids) possessing antimitotic properties were designed, synthesized and screened for their inhibitory activity against tubulin polymerization, and against proliferation of A549 lung cancer, HeLa cervical cancer, MCF7 breast cancer and HePG2 liver cancer cell lines. The design of molecules were inspired from known antimitotic compounds and natural products. The molecular docking of the designed compounds indicated that they bind to the colchicin binding site of tubulin. They were synthesized by a unique iodine catalysed oxidative ring opening reaction of 1‐aryltetrahydro‐&bgr;‐carbolines. Among the compounds synthesized quite a few compounds induced cytotoxicity on the cancer cells by disrupting the tubulin polymerization. They were found to be non‐toxic for healthy cells. Immuno Fluorescence study for the most active molecules (between ˜6&mgr;M concentration) against A549 and HeLa cells demonstrated complete disruption and shrinkage of the microtubule structures. These compounds also inhibited indoleamine‐2, 3‐dioxygenase with low micromolar IC50. HIGHLIGHTSA novel library of C2‐substituted tryptamines possessing antimitotic properties were designedMolecular docking indicated that designed molecules bind at the colchicine binding site of tubulin.The compounds are synthesized by a unique iodine catalysed oxidative ring opening reaction of 1‐aryltetrahydro‐&bgr;‐carbolines.Screened for their inhibitory activity against A549 lung cancer, HeLa cervical cancer, MCF7 breast cancer and HePG2 liver cancer cell lines.The most active compounds 17h and m, inhibited proliferation of A549, HeLa and MCF7 breast cancer with IC50 of 6–7 &mgr;M.Compounds induced cytotoxicity on the cancer cells by disrupting the tubulin polymerization.The compounds were found to be non‐toxic against WI‐38a diploid human cell line composed of fibroblasts from lung tissue.Confocal microscopy experiment for 17h and m demonstrated complete disruption and shrinkage of the microtubule structures of A549 and HeLa cells.17h and m also inhibited indoleamine‐2, 3‐dioxygenase with low micromolar IC50.