Metal complexes of naphthoquinone based ligand: synthesis, characterization, protein binding, DNA binding/cleavage and cytotoxicity studies

Abstract

Protein binding, DNA binding/cleavage and in vitro cytotoxicity studies of 2-((3-(dimethylamino)propyl)amino)naphthalene-1,4-dione (L) and its four coordinated M(II) complexes [M(II) = Co(II), Cu(II), Ni(II) and Zn(II)] have been investigated using various spectral techniques. The structure of the ligand was confirmed by spectral and single crystal XRD studies. The geometry of the complexes has been established using analytical and spectral investigations. These complexes show good binding tendency to bovine serum albumin (BSA) exhibiting high binding constant values (10 M) when compared to free ligand. Fluorescence titration studies reveal that these compounds bind strongly with CT-DNA through intercalative mode (K 10 M) and follow the order: Cu(II) > Zn(II) > Ni(II) > Co(II) > L. Molecular docking study substantiate the strength and mode of binding of these compounds with DNA. All the complexes efficiently cleaved pUC18-DNA via hydroxyl radical mechanism and the Cu(II) complex degraded the DNA completely by converting supercoiled form to linear form. The complexes demonstrate a comparable in vitro cytotoxic activity against two human cancer cell lines (MCF-7 and A-549), which is comparable with that of cisplatin. AO/EB and DAPI staining studies suggest apoptotic mode of cell death, in these cancer cells, with the compounds under investigation.

A Novel Ruthenium(II) Complex With Lapachol Induces G2/M Phase Arrest Through Aurora-B Kinase Down-Regulation and ROS-Mediated Apoptosis in Human Prostate Adenocarcinoma Cells

“…Lapachol (2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione) is a naphthoquinone, which was originally isolated from species of the Bignoniaceae family ( 5 ). We, along with other research groups, have been investigating the anticancer potential of lapachol and other naphtoquinones, free or coordinated to a metal ( 6 – 10 ). The presence of quinone group in these molecules is responsible for their outstanding known antineoplastic characteristics, including cytotoxicity, genotoxicity, and potent antitumor properties in vivo ( 11 ).…”

In vitro Analytical Techniques as Screening Tools to investigate the Metal chelate‐DNA interactions

“…[112] Along with spectroscopic changes, it can also offer information on the type of interaction seen with the DNA, nucleic acid conformation, and binding enantioselectivity. [112,[115][116][117] This technique is used to examine the non-covalent interactions of DNA with various metal complexes. The configurational and conformational changes of the system are the factors dependent on the molecule's chirality.…”

Metal Complexes as DNA Synthesis and/or Repair Inhibitors: Anticancer and Antimicrobial Agents

“…Studies on Co(II), Cu(II), Ni(II), and Zn(II) complexes of naphthoquinone have shown strong binding interaction between these compounds (Cu(II) > Zn(II) > Ni(II) > Co(II)) and DNA through an intercalative mode of binding stabilized by intermolecular hydrogen bonding. 113…”