Elevated Fibrinogen Level Reduces Therapeutic Efficiency of AD Drugs: Biophysical Insights into the Interaction of FDA-Approved Cholinesterase Inhibitors with Human Fibrinogen

• DOI: 10.1021/acs.jpcb.1c07495
• Publication Date: 2021-12-29T17:19:05Z
• Authors: Prayasee Baruah; Debojit Paul; Jitesh Doshi; Sivaprasad Mitra
• Keywords: Huperzine A; Cholinesterase; Tacrine; Butyrylcholinesterase; IC50

Despite being the second most abundant protein in blood plasma, reports on interaction of drugs with fibrinogen (FIB) are relatively scarce. The effect FIB therapeutic potency four FDA-approved Alzheimer's disease drugs, namely, tacrine (TAC), donepezil (DON), eserine (ESE), and huperzine (HUP), was investigated through a combination different vitro silico experiments. efficiency inhibiting activity acetylcholinesterase (AChE) significantly reduced presence FIB. This even found to be more substantial than that for plasma protein, human serum albumin (HSA). For example, relative change IC50 TAC 65% 10 μM as opposed 43% 250 HSA. trend modulation AChE showed consistency binding sequestration FIB, therefore reducing availability free solution, identified primary cause decrease inhibition potency. study aims establish vital component, while considering effectiveness newly developed inhibitors.