Abstract
Coumarin is a benzopyrone which is widely used as an anti-coagulant, anti-oxidant, anti-cancer and also to cure arthritis, herpes, asthma and inflammation. Here, we studied the binding of synthesized coumarin derivatives with human serum albumin (HSA) at physiological pH 7.2 by using fluorescence spectroscopy, circular dichroism spectroscopy, molecular docking and molecular dynamics simulation studies. By addition of coumarin derivatives to HSA the maximum fluorescence intensity was reduced due to quenching of intrinsic fluorescence upon binding of coumarin derivatives to HSA. The binding constant and free energy were found to be 1.957±0.01×105 M−1, −7.175 Kcal M−1 for coumarin derivative (CD) enamide; 0.837±0.01×105 M−1, −6.685 Kcal M−1 for coumarin derivative (CD) enoate, and 0.606±0.01×105 M−1, −6.49 Kcal M−1 for coumarin derivative methylprop (CDM) enamide. The CD spectroscopy showed that the protein secondary structure was partially unfolded upon binding of coumarin derivatives. Further, the molecular docking studies showed that coumarin derivatives were binding to HSA at sub-domain IB with the hydrophobic interactions and also with hydrogen bond interactions. Additionally, the molecular dynamics simulations studies contributed in understanding the stability of protein-drug complex system in the aqueous solution and the conformational changes in HSA upon binding of coumarin derivatives. This study will provide insights into designing of the new inspired coumarin derivatives as therapeutic agents against many life threatening diseases.
Highlights
Coumarin is a naturally occurring benzopyrone found in variety of plants
We examined the maximum time taken by the coumarin derivatives in binding to human serum albumin (HSA) by fluorescence emission and CD spectroscopy and found that 10 min is the maximum binding time and 10 min incubation time was used for all the experiments
In the presence of different concentrations of coumarin derivatives (0.001 to 0.01 mM) with the physiological phosphate buffer pH 7.2, our results showed that, with the increasing concentrations of coumarin derivatives and a fixed concentration of HSA (0.001 mM), the maximum fluorescence (362 nm) of HSA was quenched upon binding of coumarin derivatives (Figure 2)
Summary
Coumarin is a naturally occurring benzopyrone found in variety of plants. Coumarin and its derivatives have roles as antiinflammatory, anti-coagulant, anti-retroviral, anti-arthritic, antiherpes, anti-asthmatic, and antioxidant activities [1,2,3,4,5,6,7].Their antiretroviral activity is directly linked to their inhibitory effect on HIV-1 replication. The reduction in reverse transcriptase activity was observed when HIV infected ACH-2 lymphocytes were treated with warfarin, 4-hydroxycoumarin and umbelliferone [1]. They were used as the anti-inflammatory agents as they inhibit the cyclooxygenase and 5-lipoxygenase activities which convert arachidonic acid to endoperoxides, precursors of prostaglandins and to leukotriene A4, respectively. The anti-herpes simplex virus activity was identified in 7-(carboxymethoxy)-4-methyl coumarin designed by virtual combinatorial synthesis and selected by computational screening [3]. It has been used in the treatment of lymphedema [4]. Umbelliferone acts as a scavenger of reactive oxygen species which accounts for its antioxidant property [7]
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
