Biophysical insights into interaction mechanism of cediranib with human serum albumin: In-vitro and in-silico perspectives.

Cediranib (CB), a tyrosine kinase inhibitor, exhibits encouraging anticancer activity against breast, prostate, glioblastoma, and non-small cell lung cancer cells. This study used multi-spectral and computational analyses to elucidate the binding mechanism of CB to human serum albumin (HSA). The HSA fluorescence was substantially quenched upon CB binding and a static quenching mode was detected. An intermediate binding affinity was observed to govern the CB-HSA complex formation, while H-bonds, van der Waals, and hydrophobic interactions were supposed to stabilize the complex. The presence of CB in HSA solutions triggered variations in the secondary and tertiary structures of HSA as well as alterations in the microenvironment close to the protein fluorophores. The CB binding to HSA enhanced the protein's tolerance to thermal stress, and the addition of common metal ions to the reaction mixture resulted in minor deviations in the binding affinity of CB for HSA. The preferred binding pose of CB was positioned at Sudlow's site I of HSA, and the CB-HSA complex bound at site I persisted compact and stable through hydrogen bonds and hydrophobic interactions during molecular dynamics simulations. These findings offer important insights into the binding properties of CB to HSA that might be useful for pharmaceutical applications in the future.