Recent Progress and Future Potential for Metal Complexes as Anticancer Drugs Targeting G-quadruplex DNA

J.      Zhang; F.      Zhang; H.      Li; C.      Liu; J.      Xia; L.      Ma; W.      Chu; Z.      Zhang; C.      Chen; S.      Li; S.      Wang

doi:10.2174/092986712800672067

Abstract

Now cisplatin and its analogs are some of the most effective chemotherapeutic agents in clinical use as the first line of treatment in testicular and ovarian cancers. Unfortunately, they have several major drawbacks, such as cumulative toxicities of nephrotoxicity and ototoxicity, inherent or treatment-induced resistance. This has provided the motivation for developing novel metal complexes as anticancer agents with different mechanism of action. In recent years, significant attention has been devoted to the role of G-quadruplexes in cancer. It was found that the stabilization of G-quadruplexes by small molecules has been shown to inhibit the transcriptional activity of some oncogenes. Thus, the G-quadruplex motif has emerged as a promising target for the design of selective anticancer drugs. Apart from the purely organic heteroaromatic compounds reported as G-quadruplex binders, it has recently been shown that metal complexes can also interact strongly and selectively with quadruplex DNA and have potential anticancer activity. This review will highlight recent progress of the metal complexes as anticancer drugs targeting G-quadruplex DNA, and discuss their future potential in the medical fields. Considering the significant roles of the metal ions, the metal complexes will be discussed as follows:

(1) Ruthenium(II) complexes; (2) Nickel(II) complexes; (3) Zinc(II) complexes; (4) Manganese(III) complexes; (5) Copper(II) complexes; (6) Palladium(II)/Platinum(II); (7) Other metal complexes.

Keywords: Metal complexes as anticancer drugs, ruthenium(II) complexes, nickel(II) complexes, zinc(II) complexes, manganese(III) complexes, Copper(II) complexes, Palladium(II)/platinum(II) complexes, G-quadruplex DNA, nephrotoxicity