Issue 94, 2016

Interaction of an anticancer drug, gefitinib with human serum albumin: insights from fluorescence spectroscopy and computational modeling analysis

Abstract

Binding of gefitinib (GEF), a promising anticancer drug to human serum albumin (HSA), the major transport protein in blood circulation was investigated using fluorescence, UV-vis absorption and circular dichroism (CD) spectroscopy as well as computational modeling. Fluorescence quenching of HSA upon GEF addition was found to be a static quenching process, as revealed from the decreasing trend of the Stern–Volmer quenching constant with increasing temperature as well as UV-vis absorption spectral results. Fluorescence quenching titration results demonstrated moderate binding affinity with the binding constant, Ka value as 1.70 × 104 M−1 between GEF and HSA at 15 °C. Thermodynamic data (ΔH = −7.74 kJ mol−1 and ΔS = +54.06 J mol−1 K−1) suggested participation of both hydrophobic interactions and hydrogen bonds in stabilizing the GEF–HSA complex, which was further supported by computational modeling results. The far-UV and the near-UV CD spectra showed secondary and tertiary structural changes in HSA, whereas three-dimensional fluorescence spectral results indicated microenvironmental perturbations around protein fluorophores upon GEF binding. Binding of GEF to HSA offered significant protection to the protein against thermal destabilization. Competitive site-marker displacement results along with computational modeling analysis suggested a preferred location of the GEF binding site as site III, located in subdomain IB of HSA. Some common metal ions have been found to interfere with GEF–HSA interaction.

Graphical abstract: Interaction of an anticancer drug, gefitinib with human serum albumin: insights from fluorescence spectroscopy and computational modeling analysis

Supplementary files

Article information

Article type
Paper
Submitted
09 maí 2016
Accepted
19 sep. 2016
First published
19 sep. 2016

RSC Adv., 2016,6, 91756-91767

Interaction of an anticancer drug, gefitinib with human serum albumin: insights from fluorescence spectroscopy and computational modeling analysis

Md. Z. Kabir, W. Tee, S. B. Mohamad, Z. Alias and S. Tayyab, RSC Adv., 2016, 6, 91756 DOI: 10.1039/C6RA12019A

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