Modulated photophysical properties and sequestration of potent anti-acetylcholinesterase active coumarinyl dyes in human serum albumin

Multi-pronged spectroscopic techniques were employed to provide quantitative inputs on the modulated photophysics of nine coumarinyl derivatives in an array of solvents. Significant solvatochromic effect on the spectral behavior of the investigated systems was quantified using multiparametric regression analysis along with Density Functional Theory (DFT) calculations. The optical properties of the compounds were seen to be contingent on solvent polarity/polarizability and hydrogen bonding to varying degrees. Assessment of in-vitro antiacetylcholinesterase (AChE) activity of the investigated systems indicates their efficacy to be even better than FDA approved drug donepezil to treat Alzheimer's disease (AD) and shed novel insights into the biomedical applications of coumarinyl compounds. Interestingly, the AChE inhibition capacity of these compounds showed significant diminution in presence of human serum albumin (HSA), the principal transport protein in blood serum and therefore, reinstated its ability to modulate the therapeutic efficacies of potential drugs. The observed results were validated by quantifying the interaction of the investigated systems with HSA and also investigated through steady state and time-resolved fluorescence spectroscopy along with several other bio-analytical tools. A combination of static and dynamic mechanisms was responsible for the quenching of intrinsic protein fluorescence due to the strong sequestration ability of these coumarin derivatives into the protein binding domain. The observed results emphasized on the need of screening the pharmacological effectiveness of proposed drugs in biologically relevant media rather than in pure buffer.