Prioritization of natural compounds against mycobacterium tuberculosis 3-dehydroquinate dehydratase: A combined in-silico and in-vitro study

Enormous efforts have been endeavored to develop inhibitors against the potential therapeutic target, mycobacterium tuberculosis 3-dehydroquinate dehydratase (MtbDHQase) to combat resistance. Over a dozen of small molecules have been crystallized to characterize the structural basis of the inhibition. However, the studies accomplished so far, have not incorporated all the essential interactions of these complexes simultaneously, to identify the novel inhibitors. Therefore, an attempt was made to construct the pharmacophore models and identify the essential features that can be employed to prioritize the molecules against this target. Based on validation and expertise, we have identified such complimentary features from the natural compounds that can be used as initial hits. Subsequently, these hits were tested for their inhibitory roles in reducing the mycobacterium tuberculosis (Mtb) culture growth. Moreover, the docking simulations were performed to seek the possible interactions accountable for the activity of these candidates against MtbDHQase. [Display omitted] •Construction of pharmacophore hypotheses on the basis of co-crystal conformation of the ligands.•Identification of the diverse scaffolds from the natural compounds via multiple pharmacophores.•In-vitro evaluation of the selected natural compounds against Mtb H37Rv and prioritization of the potential candidates.