Inhibition of nucleation and disruption of amyloid fibrillation in human lysozyme aggregation by a potent Cu(II) flufenamate chemotherapeutic drug candidate.

Amyloid fibrillation is a key feature in the pathogenesis of various protein misfolding diseases. This process is driven by both primary and secondary nucleation mechanisms. Many small molecules are known to modulate protein aggregation, with certain anticancer drugs demonstrating the ability to interfere with amyloid formation. In lieu of above rationale, with the aim to repurpose anticancer drugs for other therapeutic remedies, we investigated the potential of an ionic anticancer chemotherapeutic drug candidate, namely aquachlorobis(DACH)copper(II) flufenamate complex; [{Cu(DACH)2(H2O)Cl}.(fluf)] for the inhibition of amyloid formation in Human lysozyme protein. Utilizing various biophysical techniques, viz., distinctive dye binding assays, confocal microscopy, and dynamic light scattering experiments, the potency of Cu(II) complex to inhibit human lysozyme fibrillation was studied. Our findings demonstrated that Cu(II) complex significantly disrupted amyloid fibrillation by targeting and inhibiting both primary and secondary nucleation pathways. The results indicated the high effectiveness of Cu(II) complex in preventing Human Lysozyme fibrillation, making it a promising candidate for addressing amyloidosis and paving a way for repurposing anticancer drug scaffolds as anti-AD agents.