in-silico investigation of tubulin binding modes of a series of novel antiproliferative spiroisoxazoline compounds using docking studies

interference with microtubule polymerization results in cell cycle arrest leading to cell death. colchicine is a well-known microtubule polymerization inhibitor which does so by binding to a specific site on tubulin. a set of 3',4'-bis (substituted phenyl)-4'h-spiro[indene-2,5'-isoxazol]-1(3h)-one derivatives with known antiproliferative activities were evaluated for their tubulin binding modes. 3d structures of the derivatives were docked into the colchicine binding site of tubulin using gold 5.0 program under flexible ligand and semi-flexible receptor condition. the spiroisoxazoline derivatives bind tubulin in a similar manner to colchicine by establishing at least a hydrogen bonding to cys241 as well as hydrophobic interactions with leu255, ile378 and lys254 and few other residues at the binding pocket. it can be concluded that the spiroisoxazoline core structure common to the studied derivatives is a suitable scaffold for placing the antitubulin pharmacophoric groups in appropriate spatial positions required for tubulin binding activity.