DNA-binding activity and cytotoxic and cell-cycle arrest properties of some new coumarin derivatives: a multispectral and computational investigation.

Coumarins are the most important class of natural compounds found widely in various plants. Many coumarin derivatives with different biological and pharmacological activities have been synthesized. In this study, the antiapoptotic and cytotoxic effects and DNA-binding properties of some synthetic coumarin derivatives (4b, 4d, 4f, 4 g (DBP-g), 4 h and 4j) against K562 cell lines were investigated using different techniques. MTT assay indicated that the DBP-g compound was more active than other derivatives, with a IC value of 55 μM, and therefore this compound was chosen for further investigation. Apoptosis induction was assessed using acridine orange/ethidium bromide double-staining and cell-cycle analysis. In addition, in vitro DNA-binding studies were carried out using ultraviolet-visible light absorption and fluorescence spectroscopy, as well as viscosity measurement and molecular modelling studies. In vitro results indicated that DBP-g interacted with DNA through a groove-binding mode with a binding constant (K ) of 1.17 × 10  M . In agreement with other experimental data, molecular docking studies showed that DBP-g is a minor groove binder. Overall, it can be concluded that DBP-g could be used as an effective and novel chemotherapeutic agent.