Deciphering the interaction of methotrexate with DNA: Spectroscopic and molecular docking study

Methotrexate (MTX), as one of the most significant controlling anti-rheumatism and antineoplastic medicine, which are of interest diverse pharmacological and biological activities. In this work, we determined the molecular interactions between MTX and deoxyribonucleic acid (DNA) based on the berberine (BH) as a fluorescent probe. UV–Vis spectroscopy and fluorescence studies suggested that this interaction process is predominantly a static process and intercalation of MTX into the double helix of hsDNA. The calculated negative values of enthalpy (− 60.43 kJ mol −1 ) and entropy (− 127.62 J mol −1 K −1 ) revealed that the binding reaction was predominantly driven by hydrogen bonds and van der Waals interactions. The effects of iodide quenching studies, thermal denaturation and pH on DNA-BH-MTX system were studied to support the intercalative binding of MTX with hsDNA. Furthermore, molecular docking methods further confirmed the selective binding mode between MTX and hsDNA. These findings here are expected to benefit the pharmacological testing of MTX as well as clinical research and drug screening in vitro.