Effect of Net Charge on DNA-Binding, Protein-Binding and Anticancer Properties of Copper(I) Phosphine-Diimine Complexes

Abstract

The syntheses of [Cu(PPh3)2(L)]NO3 and [Cu(PPh3)2(L-SO3Na)]NO3 were achieved through the reaction of Cu(PPh3)2NO3 and equimolar amount of the ligands (L = 5,6-diphenyl-3-[2-pyridyl]-1,2,4-triazine; LSO3Na = 5,6-diphenyl-3-[2-pyridyl]-1,2,4-triazine-4,4′-disulfonic acid disodium salt). The complexes were characterized by NMR and IR spectroscopy and mass spectrometry. The compounds exhibit similar absorption and emission spectra, suggesting a similar electronic structure. Ct-DNA binding studies show the strong influence of the net charge as Cu-L (positively charged) is able to bind to ct-DNA while Cu-LSO3Na (negatively charged) is not. The net charge of the complexes affects the thermodynamic and kinetic binding parameters toward human serum albumin. HSA-binding of the complexes was further investigated by molecular docking, revealing different binding sites on the HSA protein as a function of the net charge. The different anticancer activities of the complexes towards ovcar-3 and hope-62 cancer cell lines are suggestive of a role for the overall charge of the complexes. Interaction with the DNA is not the major mechanism for this class of complexes. The overall net charge of the pharmacophore (anticancer agent) should be a key consideration in the design of anticancer metal complexes.

Tuning anticancer properties and DNA-binding of Pt(ii) complexes via alteration of nitrogen softness/basicity of tridentate ligands

“…The hydroxy group readily dissociates to form a phenoxide moiety, resulting in an overall negative charge on the complex, so DNA binding is electrostatically unfavorable because of the strong repulsion on the backbone. 62 …”

“…The hydroxy group readily dissociates to form a phenoxide moiety, resulting in an overall negative charge on the complex, so DNA binding is electrostatically unfavorable because of the strong repulsion on the backbone. 62 (4) Three complexes display IC 50 values signicantly less (25% to 65%) than that of cisplatin: Pt-Py-OEt, Pt-PhN-OEt and Pt-PhN-NEt 2 . It seems that an ethoxy group at the 3-position of the salicylimine improves the anticancer properties compared to the other two substituents.…”

Oxazinethione Derivatives as a Precursor to Pyrazolone and Pyrimidine Derivatives: Synthesis, Biological Activities, Molecular Modeling, ADME, and Molecular Dynamics Studies

“…More than 200 pyrimidine derivatives have been used as antimicrobial agents with other mono-, di-, tri-, and tetrasubstituted classes [7]. In addition, in vitro studies of the antimicrobial activities of pyrimidine derivatives can facilitate the development of more potent and effective antimicrobial agents [8]. Some pyrimidines, especially minoxidil, are vasodilating antihypertensive agents used for resistant hypertension that is symptomatic or has caused end-organ damage, which also acted on prostaglandin G/H synthase [9].…”