Procaine is an anesthetic drug commonly administrated topically or intravenously for use in local anesthesia. Promisingly, some anticancer activities of procaine have also been reported. Therefore, the mechanism of interaction between anesthetic drug procaine with ct-DNA was determined collectively by means of various spectroscopic and molecular docking methods. Minor groove 1 : 1 binding of procaine to the ct-DNA was evidenced from absorption spectroscopy, fluorescence quenching, DNA melting, competitive binding measurements with EB and DAPI dyes, viscosity and CD spectroscopy together with molecular docking simulations and DFT calculations. Molecular docking on five different B-DNA structures (taken from the Protein Data Bank) shows that procaine binds in the AT rich region of all five B-DNA structures. Thermodynamic parameters, evaluated using van't Hoff's isotherm, shown that the interaction was feasible and the binding forces involved were hydrophobic as well as hydrogen bonding which were, further, confirmed by molecular docking. The frontier molecular orbitals (HOMO and LUMO) of procaine and DNA bases have been calculated by DFT method and the chemical potential (μ), chemical hardness (η) and fraction number of electrons (ΔN) from procaine to DNA bases were evaluated, which have shown that procaine acts as an electron donor to the DNA bases. Simultaneously, anticancer activities of procaine alone and in combination with doxorubicin were observed on the MCF-7 breast cancer cell line. The results showed that the combined treatment with both procaine and doxorubicin enhanced the cytotoxic and apoptotic inducing potential of doxorubicin.
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