Arsenic trioxide binding to serum proteins

• We model the binding of Arsenic trioxide to HSA and BSA by using the spectroscopic methods.
• We investigate the effects of drug complexation on HSA and BSA stability and conformation.
• The stronger binding was observed for BSA than HSA.
• HSA and BSA act as carrier proteins for Arsenic trioxide in delivering it to target molecules.
• At high drugs contents, significant decrease of secondary structures was observed.

Arsenic trioxide (ATO) also known as Trisenox, is an anticancer chemotherapeutic drug which has been used in treating diagnosed and relapsed patients with acute promyelocytic leukemia (APL). Serum albumin is the most abundant of the proteins in blood plasma and is the major transporter for delivering several drugs in vivo. The current study was designed to evaluate the potential ability of human and bovine serum albumin for delivering arsenic trioxide. Therefore, interaction of arsenic trioxide with HSA and BSA was investigated in aqueous solution at physiological conditions using a constant protein concentration and various drug contents. FTIR and UV–Vis spectroscopic methods were used to analyze arsenic trioxide and protein binding modes, the binding constants and the effect of drug complexation on HSA and BSA stability and conformation. Results of this study showed that drug complexation altered protein conformation by major reduction of α-helix and increase of turn structure which is indicative of a partial protein destabilization. Structural analysis revealed that arsenic trioxide bind HSA and BSA with overall binding constants of KATO-HSA = 1.07 (±0.01) × 104 M−1 and KATO-BSA = 1.27(±0.02) × 104 M−1. It could be concluded that serum albumins can be considered as good carriers for delivering arsenic trioxide to target tissue.

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