Interaction between Human Serum Albumin and antidiabetic compounds and its influence on the O2(1Δ )-mediated degradation of the protein

Abstract

The complexity depicted by disease scenarios as diabetes mellitus, constitutes a very interesting field of study when drugs and biologically relevant components may be affected by such environments. In this report, the interaction between the protein Human Serum Albumin (HSA) and two antidiabetics (Andb), Gliclazide (Gli) and Glipizide (Glip) was studied through fluorescence and docking assays, in order to characterize these systems. On the basis that HSA and Andb can be exposed in vivo at high Reactive Oxygen Species (ROS) concentrations in diabetic patients, the degradative process of the protein free and bound to Andb, in presence of the species singlet molecular oxygen (O2((1)Δg)), was evaluated. Fluorescence and docking assays indicated that Gli, as well as Glip bind to HSA on two sites, with binding constants values in the order of 10(4)-10(5)M(-1). Likewise, docking assays revealed that the location of Gli or Glip on the protein may be the HSA binding sites II and III. Thermodynamic parameters showed that the interaction between HSA and Glip is a favored, enthalpically-controlled process. Oxygen uptake experiments indicated that Glip is less photooxidizable than Gli through a O2((1)Δg)-mediated process. Besides, the protein-Andb binding produced a decrease in the overall rate constant for O2((1)Δg) quenching as compared to the value for the free protein. This fact could be interpreted in terms of a reduction in the availability of Tyrosine residues in the bonded protein, with a concomitant decrease in the physical quenching deactivation of the oxidative species.

Reactive Oxygen Species‐mediated Degradation of Antidiabetic Compounds: Cytotoxic Implications of Their Photodegradation Products

“…Specifically, O 2 ( 1 Δ g ) participated in the Rfsensitized photodegradation of both Andb, and also O ÁÀ 2 in the case of Gli. Besides, Gli showed higher reactivity than Glip against O 2 ( 1 Δ g ), as was shown in a previous contribution (39).…”

“…As was demonstrated, O 2 ( 1 Δ g ) participates in the Rf-sensitized photodegradation of both Andb. In previous studies, the specific O 2 ( 1 Δ g )-mediated degradation of Gli and Glip was investigated, employing the artificial dye PN as O 2 ( 1 Δ g )-sensitizer (39). From these studies, it was observed that the value of the rate constant of the overall O 2 ( 1 Δ g ) deactivation (k t = k q + k r , which accounts for the physical, k q , and reactive, k r , contribution to the overall deactivation, respectively) is greater for Gli than for Glip.…”

“…These results suggest that Gli is more effective than Glip in O 2 ( 1 Δ g ) deactivation. Furthermore, from reactive contribution evaluated through relative oxygen consumption rates (v r ), it can be noticed that Gli seems to be more reactive than Glip (39). Therefore, based on the greater reactivity observed between O 2 ( 1 Δ g ) and Gli, and with the aim of complete previous investigations, an HPLC mass spectrometry study of the products derived from this reaction was performed in this contribution.…”

Influence of pH and micellar systems on the sensitized photo‐oxidation of bovine serum albumin

“…Considering this observation together with the fact that no association was registered between the photosensitizer PN and human serum albumin, a very similar protein to BSA, and with other proteins, PN, that generates O 2 ( 1 △ g ) in water with a quantum yield of approximately 1, was selected as photosensitizer for all photo‐oxidation experiments in the present investigation.…”

Comparison and analysis on the serum‐binding characteristics of aspirin–zinc complex and aspirin

“…Protein binding refers to the ability of a drug molecule to interact with proteins through reversible or irreversible processes. The biological properties of a drug are highly dependent on its ability to bind to protein, which has important roles in enzymatic action, hormone activity, genic regulation and drug transport . Because of this, probing the protein‐binding properties of AZN is of great significance.…”