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.
Keywords: DNA binding; Pioglitazone; electrostatic interactions; groove binding; noncovalent interactions.
© 2018 John Wiley & Sons, Ltd.