Hyderabad: Prof. Ashwini Kumar Nangia, a Senior Professor of Chemistry at the University of Hyderabad (UoH) has published a ‘novel approach which will accelerate the discovery and development of high bioavailability drugs’.
The present-day model of drug discovery is based on identifying molecular pharmacophores, which are bioactive structural units in molecules tested for pharmacological action. However, over 80 percent of drugs are formulated as tablets or capsules and more than 90 percent of pharmaceutical lead compounds in clinical development suffer from poor bioavailability
due to low solubility and/or low permeability.
In order to address overcoming the bioavailability challenge in drug molecule lead discovery and optimization of a marketable formulation, the new model invokes the supramolecular heterosynthon in addition to the molecular pharmacophore. By refining both molecular functional groups and hydrogen bonding syn- thons, with the latter imparting high solubility and permeability in the same molecule, the overall drug discovery cycle will be accelerated compared to the traditional two-stage process.
By searching drug molecules and crystal structure databases and culling the voluminous data using artificial intelligence and machine learning tools, a medicinal chemist should be able to rationally sift the structural information and reach the target drug molecules of high bioavailability more efficiently and with a higher success rate.
The novel hybrid model has appeared as a Scientific Perspective in the Wiley international journal Angewandte Chemie of the German Chemical Society. The success of the supramolecular synthon and crystal engineering strategy in the design and development of novel salt-cocrystal drugs was recently published as an exhaustive review by Prof. Nangia in the American Chemical Society Journal of Chemical Reviews.
These dual papers, which simultaneously optimize the core of medicinal activity (pharmacophore) along with drug bioavailability (heterosynthon), will pro- vide an efficient and expeditious roadmap for the academic and pharmaceutical community.UoH Vice-Chancellor Prof. B J Rao, said, “Defining the concepts of “pharmacophore” and “heterosynthon” have been central to describing the core of drug discovery and drug bioavailability dynamics in the pharmaceutical industry.
