Multi spectroscopic and molecular simulation studies of propyl acridone binding to calf thymus DNA in the presence of electromagnetic force

Abstract

Introduction: Here, the interaction behavior between propyl acridones (PA) and calf thymus DNA (ct-DNA) has been investigated to attain the features of the binding behavior of PA with ct-DNA, which includes specific binding sites, modes, and constants. Furthermore, the effects of PA on the conformation of ct-DNA seem to be quite significant for comprehending the medicine's mechanism of action and pharmacokinetics. Methods: The project was accomplished through means of absorbance studies, fluorescence spectroscopy, circular dichroism, viscosity measurement, thermal melting, and molecular modeling techniques. Results: The intercalation of PA has been suggested by fluorescence quenching and viscosity measurements results while the thermal melting and circular dichroism studies have confirmed the thermal stabilization and conformational changes that seem to be associated with the binding. The binding constants of ct-DNA-PA complex, in the absence and presence of EMF, have been evaluated to be 6.19 × 10⁴ M^-1 and 2.95 × 10⁴ M^-1 at 298 K, respectively. In the absence of EMF, the ∆H⁰ and ∆S⁰ values that occur in the interaction process of PA with ct-DNA have been measured to be -11.81 kJ.mol^-1 and 51.01 J.mol^-1K^-1, while in the presence of EMF they were observed to be -23.34 kJ.mol^-1 and 7.49 J.mol^-1K^-1, respectively. These numbers indicate the involvement of multiple non-covalent interactions in the binding procedure. In a parallel study, DNA-PA interactions have been monitored by molecular dynamics simulations; their results have demonstrated DNA stability with increasing concentrations of PA, as well as calculated bindings of theoretical ΔG⁰. Conclusion: The complex formation between PA and ct-DNA has been investigated in the presence and absence of EMF through the multi spectroscopic techniques and MD simulation. These findings have been observed to be parallel to the results of KI and NaCl quenching studies, as well as the competitive displacement with EB and AO. According to thermodynamic parameters, electrostatic interactions stand as the main energy that binds PA to ct-DNA. Regarding the cases that involve the T_m of ct-DNA, EMF has proved to increase the stability of binding between PA and ct-DNA.

Keywords: Anti-cancer drug; Intercalator; Molecular dynamics; Propyl acridon; Spectroscopy; ct-DNA.