On the Biophysical Investigation of Sulfamethazine‐Hemoglobin Binding and the Resulting Adverse Effects of Antibiotics

Abstract

Binding of the well-known antibiotic drug sulfamethazine (SMZ) with tetrameric heme protein, hemoglobin (Hb), was studied using spectroscopic, calorimetric and molecular docking techniques. SMZ belongs to the sulfonamide group of medicines with versatile applications. Nevertheless, it can be biologically harmful if used in excess or in an uncontrolled manner. The binding induced absorbance and fluorescence data indicated a ground state complex formation between the drug and the protein with 1 : 1 stoichiometry. Drug induced conformational perturbation of Hb structure was investigated with circular dichroism and synchronous fluorescence. The binding constant obtained from spectroscopy was in the order of 10 4 M À 1 which was further confirmed by isothermal titration calorimetry. This may be higher compared to that of the oxygenation in Hb; thus SMZ binding can subsequently interrupt the oxygen transporting property of this iron protein. FRET analysis showed that the distance between SMZ and Hb is ∼ 3.75 nm, which is suitable for an effective binding. The MD simulation substantiated the mode and site of binding by confirming the factors contributing to the binding energy. It shows that SMZ binds to the central cavity close to subunit α 1helix of Hb. Residues around the drug forms hydrogen bonding and increases hydrophobicity to stabilize the SMZÀ Hb complex. The binding interaction appears to be dominated by H-bond formation and electrostatic and hydrophobic forces. This is in agreement with the thermodynamic analyses and contributes to the binding energy.

Fortification of thermal and structural stability of hemoglobin using choline chloride-based deep eutectic solvents

“…The intrinsic fluorescence of Hb is very sensitive to the microenvironments of its residues, especially around the tryptophan (Trp) residues because of the presence of the indole ring. 36 The process of denaturation can be studied by observing changes in the maximum intensity of fluorescence ( I max ) and the maximum emission wavelength ( λ max ). The fluorescence spectra (Fig.…”

Heme Protein Binding of Sulfonamide Compounds: A Correlation Study by Spectroscopic, Calorimetric, and Computational Methods

“…However, during the transient decrease in the blood O 2 level, a high concentration of Mb allows organisms to hold their breath longer by supplying O 2 to the organism. The main function of Mb succeeds only after receiving oxygen from red blood cells (hemoglobin (Hb)), transporting it to the mitochondria of the red muscle cells to produce energy. , The previous study presents the interaction pattern of the drug with Hb; this work describes further the binding of the drugs with heme protein Mb . There are several reports on the interaction study of Mb with antibiotic drugs such as ciprofloxacin, promazine, amoxicillin, aspirin, sodium penicillin, sodium cloxacillin, and sodium dicloxacillin. − However, its interaction study with sulfonamide group drugs is not known yet; hence, this directed us to study the undiscovered heme protein–sulfonamide drug interaction.…”

“…22,23 The previous study presents the interaction pattern of the drug with Hb; this work describes further the binding of the drugs with heme protein Mb. 24 There are several reports on the interaction study of Mb with antibiotic drugs such as ciprofloxacin, promazine, amoxicillin, aspirin, sodium penicillin, sodium cloxacillin, and sodium dicloxacillin. 25−27 However, its interaction study with sulfonamide group drugs is not known yet; hence, this directed us to study the undiscovered heme protein−sulfonamide drug interaction.…”

In vitro solubilization of antibiotic drug sulfamethazine: An investigation on drug–micelle aggregate formation by spectroscopic and scattering techniques

“…The interaction of SMZ with CTAB and SDS micelle formation was monitored using absorption spectroscopy (Mavani et al, 2018). SMZ showed a characteristic UV–visible absorption spectra in the range 200–300 nm with band maxima around 240 and 260 nm respectively (Fotouhi & Zabeti, 2016; Nassar et al, 2017; Ovung et al, 2020; Rajendiran & Thulasidhasan, 2015). The magnitude of the hypochromic and hyperchromic shifts, observed in each case are presented in Figure 2a,c respectively.…”