(663.1) A computational analysis of colchicine structural analogs as potential microtubule destabilizing agents

Poster Board Number: A259

Isadora Rocha De Abreu (Nova Southeastern University, Institute for Neuro-Immune Medicine), Allison Barkdull (University of Florida), Travis Craddock (Nova Southeastern University, Institute for Neuro-Immune Medicine, Nova Southeastern University)

Microtubules are important for the formation of the cytoskeleton and mitotic spindles, and they aid in cell movement and intracellular transport. Therefore, they are important for cell survival and cell function. Microtubules are composed of the alpha-beta tubulin heterodimer protein. During polymerization tubulin proteins experience phases of dynamic instability, which is characterized by microtubule growth and shrinkage at varying rates. Microtubule formation can be inhibited by compounds such as colchicine, a known microtubule destabilizing agent, that binds to tubulin to block polymerization. In this study we investigated one hundred eleven compounds that had a similar structure to colchicine. We used AutoDock Vina to dock each compound including colchicine to tubulin in the same binding site as colchicine. The binding energy of colchicine was -10.9 kcal/mol, and the binding energies of the top 10% binding affinity compounds were between -9 kcal/mol and -7.9 kcal/mol. The pharmacokinetic properties of these drugs, computational binding affinity and similarity to colchicine show promise as novel inhibitors of microtubule polymerization, which will be further explored through laboratory experiments.