Abstract
β-Carbolines (βCs) belong to the naturally occurring alkaloid family, derived from 9H-pyrido[3,4-b]indole, also known as norharmane (Hnor). Knowing the importance of the βCs alkaloid family in biological processes, a comprehensive binding study is reported of four Ag(I) compounds containing the ligand Hnor and having different counteranions, namely, NO3 −, ClO4 −, BF4 −, and PF6 −, with human serum albumin (HSA) as a model protein. Different approaches like UV-visible, fluorescence spectroscopy, circular dichroism (CD), and molecular docking studies have been used for this purpose. The fluorescence results establish that the phenomenon of binding of Ag(Hnor) complexes to HSA can be deduced from the static quenching mechanism. The results showed a significant binding propensity of the used Ag(I) compounds towards HSA. The role of the counteranion on the binding of Ag(I) compounds to HSA appeared to be remarkable. Compounds with (ClO4 −) and (NO3 −) were found to have the most efficient binding towards HSA as compared to BF4 −and PF6 −. Circular dichroism (CD) studies made clear that conformational changes in the secondary structure of HSA were induced by the presence of Ag(I) compounds. Also, the α-helical structure of HSA was found to get transformed into a β-sheeted structure. Interestingly, (ClO4 −) and (NO3 −) compounds were found to induce most substantial changes in the secondary structure of HSA. The outcome of this study may contribute to understanding the propensity of proteins involved in neurological diseases (such as Alzheimer's and Parkinson's diseases) to undergo a similar transition in the presence of Ag-β-carboline compounds.
Highlights
Human serum albumin (HSA) is responsible for about 60% of the plasma protein in humans and is accountable for nearly 80% of the osmotic pressure of the blood, and it plays a prominent role in drug disposition and efficacy [12]
Substituted aromatic β-carbolines may enter into the brain by crossing the blood-brain barrier (BBB) and may be converted into methyl derivatives by specific enzymes, like methyltransferases
Some β-carbolines like 2,9-dimethylβ-carbolines have exhibited mitochondrial damage leading to neurotoxicity, while 9-methyl-harmine has a neuroprotective effect. β-Carboline compounds are known to reduce the expression of phosphorylated forms of the socalled tau protein, potently at multiple Alzheimer’s diseaserelated sites [17,18,19,20]
Summary
Shen et al [31] have studied the interaction of Ag+ alone with HSA When we compared these results of Ag compounds with Ag+ alone, silver compounds exhibited signi cantly worthy binding propensity compared to the Ag+ alone. With the aim to gain more information about the mode of binding of the Ag(I) compounds with HSA, solution uorescence studies were carried out. E interaction of the Ag compounds with HSA was quanti ed; the Stern–Volmer equation has been employed [41]: F0 F. where F0 and F are the steady-state uorescence intensities in the absence and presence of quencher at 340 nm, respectively. By calculating the quenching rate constants, Kq, one can distinguish between the static quenching and the dynamic quenching, and this was evaluated by using the following equation: RFI RFI
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
