Pharmacophore model generation for microtubule-stabilizing anti-mitotic agents (MSAAs) against ovarian cancer

Microtubules have always remained a mainstay in the discussion of anti-cancer drugs. Research is being carried out since over a decade on the microtubule-binding agents. The already present drugs have acquired clinical disadvantages or limitations, most importantly, the acquired resistance. Microtubule-stabilizing anti-mitotic agents (MSAAs) has proved important therapeutic agents for the treatment of cancer. The development of new and potent MSAAs is of both clinical and research interests. Ligand-based pharmacophore modeling is playing a key role for the identification of ligand features for the particular targets. We present a model for designing the pharmacophore onto the set of 12 compounds of 10 different classes and two FDA approved standard drugs. The ligand-based pharmacophore model with one hydrophobic or aromatic group, two Hydrogen-bond acceptors and one Hydrogen-bond donor has been identified to facilitate the discovery of highly potent MSAAs. The result indicates that the in silico methods are useful in predicting the biological activity of the compound or compound library by screening it against a predicted pharmacophore. Ligand Scout 3.02 has been used to predict the pharmacophore features for MSAAs and the distances between pharmacophore features have been calculated through the software VMD. This discovery will help in the identification of more potent MSAAs.