Synthesis, Characterization, and DNA Binding Studies of a New Pt(II) Complex Containing the Drug Levetiracetam: Combining Experimental and Computational Methods

Abstract

The water-soluble platinum(II) complex, [Pt(LV)(dmso)Cl]Cl (LV is Levetiracetam an anti-epileptic drug belonging to the pyrrolidine family) was synthesized and characterized using physico-chemical, spectroscopic and computational methods. Multi-spectroscopic methods used to study the interaction of Pt(II) complex with calf thymus (ct-DNA) in Tris-HCl buffer solution (pH 7.4). The Pt(II) complex was found to be a minor groove binder with a preference for the A-T region compared to the G-C region. This was substantiated by displacement studies with Hoechst 33258, a known minor groove binder. The mean binding constant obtained from the spectroscopic techniques was 7 × 10(4) M(-1). In comparison with the previous study, the binding constant of Pt(II) complex is 15 times greater than the corresponding value of levetiracetam. These results indicate that the binding affinity of Pt(II) complex is stronger than levetiracetam.

A structural and biological study on the new 3,5-diacetyl-1,2,4-triazol bis(p-chlorophenylthiosemicarbazone) ligand and its bimetallic complexes

“…The K b values obtained here are lower than that reported for double-stranded DNA intercalators while they are comparable to other classical groove binders. 34,35 Therefore, these findings support the interaction of both compounds with DNA via groove binding.…”

“…While measuring the absorption spectra, an equal amount of CT DNA was added to both the test solution and the reference solution to eliminate the absorbance of CT DNA itself. The data were then fitted to the following equation 33 : 34,35 Therefore, these findings support the interaction of both compounds to DNA via groove binding. Taking in account that both the free ligand and the platinum complex have demonstrated similar cytotoxic activity, it seems that DNA interactions is not the unique responsible for inhibition of cell proliferation.…”

Studying non-covalent drug–DNA interactions

“…In case of groove binders, competitive displacement studies are done using Hoechst 33258 that binds to the minor groove of double stranded B-DNA and has high specificity for AT-rich sequences [47]. Hoechst 33258, on binding with DNA, shows enhancement in the fluorescent intensity [48][49][50].…”

The in Vitro Antiplasmodial and Antiproliferative Activity of New Ferrocene‐Based α‐Aminocresols Targeting Hemozoin Inhibition and DNA Interaction

“…Employing previously described Hoechst (DNA minorgroove binder) and methylene blue (DNA intercalator) competitive DNA binding assays, interrogation of the binding mode of compound 9 a was undertaken. [23,46,47] Hoechst 33342, a confirmed DNA minor-groove binder, produces an intense fluorescence emission at 460-485 nm when bound to DNA. [48,49] In the presence of a competing DNA minor-groove binder, the DNA-bound Hoechst 33342 dye molecules will be competitively displaced from the DNA structure, leading to fluorescence attenuation.…”