Donor-acceptor functionalized coumarin derivatives: Synthesis, fluorescence modulation, interaction with human serum albumin and acetylcholinesterase inhibition activity

Abstract

A coumarin compound 7-diethylaminocoumarin (DEAC) and its substituted derivative coumarin-6-CF3 (CCF3) were synthesized, characterized and their photophysical behavior have been investigated by steady state and time resolved fluorescence spectroscopy. Both the investigated systems show appreciable modulation in photophysical properties depending on the nature of the solvent medium and in presence of sequestering agents like cyclodextrin nanocavities and/or human serum albumin (HSA). Quantitative estimation of different solvent parameters responsible for the modulated spectral features were done from multiple linear regression analysis of the experimental data based on Kamlet-Taft and Catalán formalisms. Significant modulation in fluorescence quantum yield in polar-protic medium and/or highly viscous glycerol solution for CCF3 in comparison with the model compound DEAC was due to donor–acceptor functionalization in the former. This additional excited state charge transfer possibility led to very large excited state dipole moment change in CCF3 and resulted almost ∼ 90 nm solvent dependent fluorescence peak shift. Multi-pronged experimental results in conjunction with molecular docking calculation revealed moderate binding affinity of the investigated systems towards HSA. Additionally, the coumarin derivatives were evaluated for its anticholinergic activity using in-vitro acetylcholinesterase enzymatic assay. The results demonstrated a significant inhibition of cholinergic activity, particularly for donor–acceptor functionalized CCF3, highlighting the potential therapeutic application of it. The study provides important insights into the molecular interactions and pharmacological properties of these promising coumarin derivatives, which could serve as a basis for the development of new drug candidates targeting cholinergic pathways.