Interaction between Antimalarial 2-Aryl-3H-indol-3-one Derivatives and Human Serum Albumin

Abstract

Binding of drugs to plasma proteins, such as albumin, is a major factor which determines their pharmacokinetics and pharmacological effects. Therefore, the interactions between human serum albumin (HSA) and four antimalarial compounds selected in the 2-aryl-3H-indol-3-one series have been investigated using UV-visible, fluorescence and circular dichroism (CD) spectroscopies. Compounds produced a static quenching of the intrinsic fluorescence of HSA. The thermodynamic parameters have shown that the binding reaction is endothermic for three compounds while exothermic for the 2-phenyl-3H-indol-3-one, 3. The interaction is entropically driven with predominant hydrophobic forces with binding affinities of the order of 10(4) M(-1). The highest binding constant is observed for 3 (Kλ=280nm = 4.53 × 10(4) M(-1)) which is also the less active compound against Plasmodium falciparum. Synchronous fluorescence gave qualitative information on the conformational changes of HSA while quantitative data were obtained with CD. Displacement experiments with site markers indicated that drugs bind to HSA at site I (subdomain IIA). In addition, the apparent binding constant and the binding site number were calculated in the presence of different ions.

Investigation on the Interaction of Norgestrel with Human Serum Albumin Using Spectroscopy and Molecular‐Docking Method

“…Probe experiments were carried out using warfarin and ibuprofen, which explicitly bound with sites I and II, respectively . The percentage of displacement by a probe can be calculated as follows : where F and F 0 are the fluorescence intensities of norgestrel–HSA in the absence and presence of probes, respectively. Figure D shows that the fluorescence intensity of the norgestrel–HSA system was obviously changed with the warfarin concentration increased and slightly changed with increasing ibuprofen concentration.…”

“…K app d (Table 3) increased and PSH decreased for ANS-HSA after adding norgestrel, which indicated that ANS detached from HSA as norgestrel occupied some low-affinity binding sites of ANS [ 35,37]. On the other hand, the majority of bound ANS molecules existed in domain II because nearly all accessible hydrophobic residues of HSA were located there [31]. Therefore, the occupation of norgestrel to ANS implied that the binding site of norgestrel-HSA was site I, consistent with the molecular-modeling result.…”

“…Probe experiments were carried out using warfarin and ibuprofen, which explicitly bound with sites I and II, respectively [30]. The percentage of displacement by a probe can be calculated as follows [31]:…”

Combination mode of antimalarial drug mefloquine and human serum albumin: Insights from spectroscopic and docking approaches

“…[19,27,30] The interaction studies between several antimalarial drugs and serum albumins have been published, based on fluorescence and other spectroscopic techniques. [31][32][33][34] Due to the presence of another transport protein (α 1 -acid glycoprotein) in the blood plasma, binding of antimalarial drugs to α 1 -acid glycoprotein has also been reported. [35] Emission of the protein fluorescence at 343 nm, when excited at 295 nm ( Figure 1A) can be assigned to the sole Trp residue (Trp-214) of HSA, located in the subdomain IIA of the protein.…”

Probing the binding of two 19‐nortestosterone derivatives to human serum albumin: insights into the interactions of steroid hormone drugs with functional biomacromolecule

“…As the most abundant protein constituent of blood plasma, human serum albumin (HSA) can bind a wide range of endogenous and exogenous compounds and serves as an important carrier for a broad range of drugs (Ghuman et al, 2005;Zhu et al, 2015). This protein is composed of a single polypeptide chain, with three homologous α-helical domains I-III (Rakotoarivelo et al, 2014). Each domain contains two subdomains A and B, which correspond to two primary drugbinding sites, namely, sites I and II.…”