Pharmacophore-based database mining for probing fragmental drug-likeness of diketo acid analogues.

A number of the structurally diverse chemical compounds with functional diketo acid (DKA) subunit(s) have been revealed by combined online and MoStBiodat 3D pharmacophore-guided ZINC and PubChem database screening. We used the structural data available from such screening to analyse the similarities of the compounds containing the DKA fragment. Generally, the analysis by principal component analysis and self-organizing neural network approaches reveals four families of compounds complying with the chemical constitution (aromatic, aliphatic) of the compounds. From a practical point of view, similar studies may reveal potential bioisosteres of known drugs, e.g. raltegravir/elvitegravir. In this context, it seems that mono-halogenated aryl substructures with para group show the closest similarity to these compounds, in contrast to structures where the aromatic ring is halogenated in both ortho- and para-locations.