Molecular Dynamics and Multi-Spectroscopic of the Interaction Behavior between Bladder Cancer Cells and Calf Thymus DNA with Rebeccamycin: Apoptosis through the Down Regulation of PI3K/AKT Signaling Pathway.

The interaction of Rebeccamycin with calf thymus (ctDNA) in the absence and presence of H1 was investigated by molecular dynamics, multi-spectroscopic, and cellular techniques. According to fluorescence and circular dichroism spectroscopies, Rebeccamycin interacted with ctDNA in the absence of H1 through intercalator or binding modes, while the presence of H1 resulted in revealing theintercalator, as the dominant role, and groove binding modes of ctDNA-Rebeccamycin complex. The binding constants, which were calculated to be 1.22 × 104 M-1 and 7.92 × 105 M-1 in the absence and presence of H1, respectively, denoted the strong binding of Rebeccamycin with ctDNA. The binding constants of Rebeccamycin with ct DNA in the absence and presence of H1 were calculated at 298, 303 and 308 K. Considering the thermodynamic parameters (ΔH0 and ΔS0), both vander waals forces and hydrogen bonds played predominant roles throughout the binding of Rebeccamycin to ctDNA in the absence and presence of H1. The outcomes of circular dichroism suggested the lack of any major conformational changes in ctDNA upon interacting with Rebeccamycin, except some perturbations in native B-DNA at local level. Additionally, the effect of NaCl and KI on ctDNA-Rebeccamycin complex provided further evidence for the reliance of their interaction modes on substituted groups. The observed increase in the relative viscosity of ctDNA caused by the enhancement of Rebeccamycin confirmed their intercalation and groove binding modes in the absence and presence of H1. Moreover, the assessments of molecular docking simulation corroborated these experimental results and also elucidated the effectiveness of Rebeccamycinin inhibiting and proliferating T24 and 5637 cells. Meanwhile, the ability of Rebeccamycin in inhibiting cell proliferation and tumor growth through the induction of apoptosis by down regulating the PI3K/AKT signaling pathway were provided.

Description of the calf thymus DNA-malathion complex behavior by multi-spectroscopic and molecular modeling techniques: EMF at low and high frequency approaches.

OBJECTIVES: Small molecules can bind to DNA via covalent or non-covalent interactions, which results in altering or inhibiting the function of DNA. Thus, understanding the interaction patterns of medicines or other small molecules can be very crucial. In this study, the interaction between malathion and calf thymus DNA (ctDNA), in the absence and presence of electromagnetic field (EMF) at low and high frequencies, was investigated through various spectroscopies and viscosity measurements. MATERIALS AND METHODS: The interaction studies were performed by means of absorbance, circular dichroism, fluorescence spectroscopy, viscosity, thermal melting, and molecular modeling techniques. RESULTS: The fluorescence intensity of the ctDNA-malathion complex in the presence of EMF, has revealed quenching of fluorescence emission curves. The dynamic interaction and RLS studies have implied the changes in ctDNA-malathion complex throughout the presence of EMF which suggested that hydrophobic forces play the main role in the binding. Studies have revealed that malathion does not have any effect on binding ethidium bromide to ctDNA, which signifies the groove binding. The viscosity of ctDNA increased as the malathion concentration was enlarged. The circular dichroism technique suggested that the ellipticity values of the ctDNA-malathion complex have not increased with enhancing the malathion concentration. Molecular docking and dynamics studies have indicated a potent electrostatic interaction between ctDNA and malathion in the groove binding site. CONCLUSION: The results of spectroscopic studies reinforced a potent interaction between malathion and ctDNA in the absence and presence of EMF which can help us for further pharmaceutical drug discoveries.