Spectroscopic studies of interactions of 2-(2-Oxo-2-Phenylethyl)-1,2-benzisothiazol-3(2H)-one-1,1-dioxide with human DNA
Abstract
The interaction of small molecules with DNA has become the most prominent area of research for the discovery of new drugs that may be helpful in curing of the diseases. The present research work was designed to explore the interactions of 2-(2-Oxo-2-Phenylethyl)-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (BTZDO) with DNA by spectroscopic methods in physiological buffers of pH 4.7 and 7.4.
Spectral results showed the hypochromic and bathochromic shifts after addition of DNA. The binding constant (K-f) of 5.18 x 10(2) and 8.62 x 10(2) Lmol(-1) were determined at pH 4.7 (stomach pH) and 7.4 (blood pH) respectively.
Strong values of binding constants reflected strong complex between BTZDO and DNA. The observed values of binding constant suggested that the intake of BTZDO inside human body via blood is more effective as compared to the oral intake.
The interpretation of physical mode to intake the newly synthesized BTZDO drug into human body is the novelty of this research work. An intercalation binding of the BTZDO with DNA was supported by the results obtained from DNA melting studies.
The Gibbs free energy calculated at pH 4.7 was -15.22 kJmol(-1) and at pH 7.4 was -16.46 kJmol(-1). The negative values of free energies are the prerequisite that the binding process to be spontaneous.
Thermodynamic parameters (enthalpy and entropy) were also calculated. The enthalpy calculated for this system was -29.23 kJmol(-1)K(-1) at pH 4.7 and -52.56 kJmol(-1)K(-1) at pH 7.4.
The entropy calculated for present system at pH 4.7 was -48.22 Jmol(-1)K(-1) and at 7.4 the value was -122.89 Jmol(-1) K-1. Negative values of entropy predicted that a compact complex was formed between BTZDO and DNA.
The focal point of this investigation was the observation of the effect of temperature on binding between the BTZDO and DNA, nature of complex formed and especially, the preferred mode adopted for the intake of medicine.