Abstract
The development and design of pharmaceutical cocrystals for various biological applications has garnered significant interest. In this study, we have established methodologies for the growth of the methylparaben-quinidine cocrystal (MP-QU), which exhibits a well-defined order that favors structure-property correlation. To confirm the cocrystal formation, we subjected the cocrystals to various physicochemical analyses such as powder X-ray diffraction (PXRD), single-crystal X-ray diffraction (SCXRD), Raman, and IR spectroscopy. The results of the XRD pattern comparisons indicated no polymorphisms, and density functional theory (DFT) studies in both gaseous and liquid phases revealed enhanced stability. Our in silico docking studies demonstrated the cocrystal's high-affinity binding towards cancer-specific epidermal growth factor receptor (EGFR), Janus kinase (JAK), and other receptors. Furthermore, in vitro testing against three-dimensional (3D) spheroids of lung cancer (A549) and normal fibroblast cells (L929) demonstrated the cocrystal's higher anticancer potential, supported by cell viability measurements and live/dead assays. Interestingly, the cocrystal showed selectivity between cancerous and normal 3D spheroids. We found that the MP-QU cocrystal inhibited migration and invadopodia formation of cancer spheroids in a favorable 3D microenvironment.