Bio-physical and computational studies on serum albumin / target protein binding of a potential anti-cancer agent.

The successful evolution of an effective drug depends on its pharmacokinetics, efficiency and safety and these in turn depend on the drug-target/drug-carrier protein binding. This work, deals with the interaction of a pyridine derivative, 2-hydroxy-5-(4-methoxyphenyl)-6-phenylpyridine 3-carbonitrile (HDN) with serum albumins at physiological conditions utilizing the steady state and time-resolved fluorescence techniques by probing the emission behavior of Trp in BSA and HSA. In-silico studies revealed a combined static and dynamic quenching mechanism for the interactions. The binding studies suggests a spontaneous binding between HDN and the albumins with a moderate binding affinity (Kb ∼ 10 M-1) with a single class of binding site. The FRET mediated emission from HDN indicates preferential binding of HDN in subdomain IIA of the albumins with Trp residue in close proximity. Circular dichroism results indicate HDN induced conformational changes for BSA and HSA, but the α-helical secondary structure was well preserved even up to a concentration of 10 µM HDN. Moderate binding affinity of HDN with BSA and HSA and the unaltered secondary structure of proteins on binding propose the potential application of HDN as an efficient drug. The application of docking method on the affinity of HDN towards the proposed target/receptor is discussed.