ABSTRACT
Pioglitazone is an antidiabetic drug used to treat type 2 diabetes mellitus. Interaction of Pioglitazone with calf thymus DNA was investigated using multispectroscopic techniques and molecular docking study. Quenching and binding constant was calculated at 3 different temperatures. The binding constant of Pioglitazone with calf thymus DNA was calculated to be 6.49 × 103 M-1 at 293 K. The quenching mechanism was found to be a static process, and thermodynamic parameters revealed van der Waals interactions and hydrogen bonds to be the major force working in Pioglitazone-DNA interaction. Pioglitazone follows the nonintercalative mode of binding and was involved in complex formation with DNA through minor groove binding and electrostatic interactions. Experiments like KI quenching studies, dye displacement assays, Circular Dichroism (CD) spectroscopy, DNA melting study, and viscosity measurements studies supported the nonintercalative mode of binding. This was further corroborated by molecular docking studies.
Subject(s)
DNA/chemistry , DNA/metabolism , Hypoglycemic Agents/metabolism , Pioglitazone/metabolism , Animals , Cattle , Circular Dichroism , Hydrogen Bonding , Models, Molecular , Molecular Docking Simulation , Nucleic Acid Conformation , Nucleic Acid Denaturation , Spectrometry, Fluorescence , ThermodynamicsABSTRACT
Interaction of procarbazine (PCZ) with calf thymus DNA was studied using biophysical and molecular docking studies. Procarbazine was to interact with DNA with a binding constant of 6.52 × 103 M-1 as calculated using ultraviolet-visible spectroscopy. To find out the binding mode, molecular docking was performed that predicted PCZ to interact with DNA through groove binding mode with binding affinity of -6.7 kcal/mole. To confirm the groove binding nature, different experiments were performed. Dye displacement assays confirmed the non-intercalative binding mode. Procarbazine displaced Hoechst dye from the minor groove of DNA while it was unable to displace intercalating dyes. There was no increase in the viscosity of DNA solution in presence of PCZ. Also, negligible change in the secondary structure of DNA was observed in presence of PCZ as evident by circular dichroism spectra. Procarbazine caused decrease in the melting temperature of DNA possibly because of decrease in the stability of DNA caused by groove binding interaction of PCZ with DNA.
Subject(s)
DNA/chemistry , DNA/metabolism , Procarbazine/metabolism , Animals , Binding Sites , Cattle , Circular Dichroism , Models, Molecular , Molecular Docking Simulation , Procarbazine/chemistry , Temperature , ViscosityABSTRACT
The field of higher education has been progressing at a rapid pace in the Kingdom of Saudi Arabia over the past decade, with doubling the number of government and private universities and colleges. Quality and accreditation are of great importance to higher education institutes world-wide. Thus, developing a generic model for quality management in higher education is badly needed in the country.
