Identification of Leads from Marine Seaweeds against Human β-tubulin

Selvaa      Kumar C; Nikhil      Gadewal; Sudheer      M.M. Mohammed

Abstract

Tubulin has received more attention as potent anticancer drug target because it is the fundamental unit of microtubules and plays an active role in cell division. The drugs against β-tubulin are mainly derived from terrestrial plants and marine resources. Of these, red and brown algae from the marine environment produce better secondary metabolites. These compounds are found to be active against cancer cell lines. Since there is no study reported till date about the activity of these compounds against human β-tubulin, we have investigated the role of 517 compounds available in the seaweed secondary metabolites database against modeled human β-tubulin. All the conformers of lead compounds (RL381, RL366, RL376 and RG012) when docked at the taxol binding site showed better interactions with the H1-S2 loop and M-loop which are actively involved in lateral interactions of tubulins and also with the helix H7 which is the connecting link between N-terminal and intermediate domain. Important residues involved in polar interaction by these lead compounds were D224, H227, R276, R282 and R359 which closely mimicked the interaction of taxol with β-tubulin. We then attempted to calibrate the available molecules based on their Lipinski rule, binding affinity and other descriptor based comparison to identify potential lead molecules which could be used as drugs against human β tubulin.

Keywords: Lead molecules, Virtual screening, Tubulin, Seaweeds, Metabolites, α/β tubulin, GTPases, H8-H10, hydrophobic taxol, Paclitaxel