Role of crystal engineering in repurposing drugs for therapy of antiparasitic vector-born disease: structure-property relationship

Drug repurposing becomes an emerging approach for leveraging the utilization of the approved drugs or that what previously are investigated toward phases of clinical trail for treatment of the original diseases redirecting their well-establish pharmacokinetics and safety in validation the new therapies compared to their initial pharmacological treatments.
The identification of new opportunities for use of old drugs requires a holistic approach of innovative computational method in combination with biological testing on experimental cell/ animal models. Thus, customizing and optimizing screening potential of hit or lead compounds from existing databases using in silico calculations and subsequently confirming their activity through a series of biological experiments promise effective overcoming bottlenecks and expedite a cost-effective discovery of alternative therapeutic agents and their applications [1]. Drug repositioning accounts for approximately 30% of the newly US Food and Drug Administration (FDA)-approved drugs and vaccines in recent years.
The purpose of the presented crystal structures searched in the Cambridge Structural Database (CSD) among the insecticide class of compounds with isooxazoline molecular scaffold [2] as well Dibucaine, Phenylephrine, Acebutolol, Prilocaine, Albendazole, Ethacrynic acid, Ganciclovir, Benzthiazide, Ethionamide [3] and Praziquantel [4] repurposed for treatment of Leishmania is to reveal the opportunities for engineering new crystal phased of multicomponent crystals combining these drug compounds with ligands selected based on the best proton donor/acceptor groups and molecular moieties that guide to non-covalent interactions, mainly Hydrogen-bonds which geometry may be utilized in crystal structure prediction with enhanced water solubility [5].