Title : Anti-amyloid aggregation and anti-hyperglycemic activities of ruthenium uracil Schiff base compounds and their chitosan-polyvinyl alcohol electrospun nanofiber conjugates
Abstract:
Our earlier studies on a leading uracil-Schiff base chelated ruthenium compound, [Ru(H3ucp)Cl(PPh3)] (1) (H4ucp = 2,6-bis-((6-amino-1,3-dimethyluracilimino)methylene)pyridine) showed it can serve as a candidate metal-based drug in an anti-diabetic animal model.[1] Most recently, we have illustrated that the structural features of 1 and its derivatives dictate their mechanism of anti-diabetic action.[2] Solution chemical reactivities of the different ruthenium complexes were rationalized by density functional theory computations. Furthermore, the binding affinities and strengths between BSA and the respective ruthenium complexes were monitored using fluorescence spectroscopy. The diimine bis-uracil metal complexes could disintegrate mature amylin amyloid fibrils, while the mono-imine uracil metal complexes showed comparable disaggregation capabilities for the BSA (ThT) amyloidal plaques. In addition, the in vitro anti-diabetic activities of the novel metal complexes were assessed in selected skeletal muscle and liver cell lines. In the pursuit to develop proficient metallopharmaceuticals for Diabetes Mellitus (DM), the lead metal complex and its analogs were individually incorporated into nano-confined polymer frameworks to investigate their corresponding drug-release profiles and glucose-lowering effects in selected cell lines in a time-dependent manner. In particular, chitosan (CS)-polyvinyl alcohol (PVA) electrospun nanofibers (CS-PVA ENFs) containing the different ruthenium uracilimino complexes (Ru) were fabricated by in situ electrospinning. The resultant guest-host nanoconjugates were characterized by Scanning Electron Microscopy - Energy Dispersive X-ray (SEM-EDX), powder X-ray diffraction, and FTIR spectroscopy.
