How can the cisplatin analogs with different amine act on DNA during cancer treatment theoretically?

Cisplatin is a widely used anti-cancer drug which inhibits the replication and polymerization of DNA molecule while showing some side effects and drug resistance. For this reason, to enhance its therapeutic index, researchers have synthesized several thousand analogs and tested their properties. In this project, several cisplatin analogs were designed to theoretically study the biological activity and lipophilicity effects on amine changes. The amines of the cisplatin molecule were substituted with aliphatic amines in different analogs. Computational methods such as molecular dynamics simulation, molecular docking, and molecular mechanics Poisson-Boltzmann surface area analysis were performed to investigate the binding of six cisplatin derivatives with DNA. The binding affinity and potential interactions of these drugs with double-strand DNA were analyzed. The stability effect of these drugs was investigated via root-mean-square deviation and root-mean-square fluctuation analysis, which showed that some analogs can break base-pair interaction at the end of DNA and reduced the stability of DNA. Also, the results revealed that the hydrogen bond is one of the most important factors in the binding of cisplatin's adduct to DNA. Molecular mechanics Poisson-Boltzmann surface area analysis indicated that electrostatic and van der Waals interactions are the most important deriving forces to the binding of cisplatin's drug to DNA. Finally, data revealed that cisplatin and the cis-dichloro-dimethylamine-platin tendency for binding to DNA are greater than that of other analogs.

Anticancer activity of novel amino acid derivative of palladium complex with phendione ligand against of human colon cancer cell line.

The aim of this work is the identification of the structural effect of amino acid-Pd complex on DNA as an intracellular target which was studied using various spectroscopic techniques such as fluorescence, UV-visible and circular dichroism in combination with a molecular docking study. Hence, a novel water-soluble palladium complex, [Pd(phendione)(isopentylglycine)]NO3, has been synthesized and characterized by spectroscopic method. The anticancer activity of complex was investigated against human colon cancer cell line of HCT116 after 24 h of incubation using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. In addition, this complex was interacted with calf thymus DNA (ct-DNA) via positive cooperative interaction. The fluorescence data indicate that Pd complex is intercalated in DNA. These results were confirmed by circular dichroism spectra. The molecular docking results indicate that docking may be an appropriate method for the prediction and confirmation of experimental results. Complementary molecular docking results may be useful for the determination of the binding mechanism of DNA in pharmaceutical and biophysical studies providing new insight into the novel pharmacology and new solutions in the formulation of advanced oral drug delivery systems. Docking and spectroscopic studies show that new water-soluble Pd complex has anticancer activity and it can bind to DNA via intercalation and groove binding.