Heterocycle Tethered Ferrocenyl Conjugates as Potential Inhibitor Against Fibrillation of Amyloidogenic Proteins: Solvent Free Synthesis, Structure, MD Simulation Study

Abstract

Molecular scaffold containing organometallic fragments linked to heterocycle shows their potency as therapeutics against major diseases and can play a vital role as tracers in mmunological analysis based on several analytical methods.1Selective fictionalization of electro active ferrocenyl moiety with Heterocycles provide molecular system with potential features related to chemo- and bio-sensors, protein binding interaction, varied biological activity.2 To accomplish facile fictionalization of ferrocenyl moiety, solvent free, redmud supported reaction was carried out for selective fictionalization to obtain bis-pyridyl and bis-pyrazinyl incorporated ferrocenyl enone conjugates. The solid supported reaction also gave a rarely known ferrocene based 1,4- Michael addition product containing bis-pyridyl moieties. Spectroscopic characterization and structural confirmation have been carried out using IR, NMR and single crystal X-ray diffraction study. Molecular docking study of the Fc-heterocyclic compounds revealed significant hydrogen binding interaction with proteins at their amyloidogenic regions. The compounds showed marked inhibitory potential against amyloid fibrillation and disaggregation process in BSA and HEWL proteins. Concentration dependent ThT assay, DLS measurement, TEM, CD etc. have been carried out to monitor the inhibitory potencyof these ferrocenyl conjugates.