Antitumor Activity and DNA-Binding Investigations of the Zn(II) and Cu(II) Complexes with Isoeuxanthone

Abstract

Recently, more and more attention has been paid to xanthones that are widely present as a class of secondary metabolites in some higher plants and microorganisms. [1][2][3] These naturally occurring compounds and their synthetic analogs have been reported to exhibit multiple important pharmacological properties, such as anti-oxidant, anti-inflammatory, anti-malarial and anti-cancer activity, etc. [4][5][6][7][8][9] As shown in Fig. 1a, xanthones having three linear fused aromatic rings may be viewed as flavone derivatives in which the phenyl group is fused with the two aromatic rings. This structural 'similarity,' together with the aforementioned studies on hydroxyflavones and biological efficacy of xanthones enforced many scientists to isolate or synthesize appropriately modified derivatives for the development of prospective new drug candidates.10-12) Isoeuxanthone (Fig. 1b) is one of well-known xanthone derivatives which have diverse biological profiles.Since DNA is an important cellular receptor, many chemicals exert their antitumor effects to DNA thereby changing the replication of DNA and inhibiting the growth of the tumor cell, which is the basis of designing new and more efficient antitcancer drugs and their effectiveness depends on the mode and affinity of the binding.13) Similarly, interactions of metallic antitumor reagents with DNA are also very important in understanding the mechanisms of their antitumor activities.14,15) We were thus motivated to investigate metallic complexes of isoeuxanthone on their binding modes and affinities to DNA. Therefore, in this context, we report the synthesis and characterization of the mononuclear Zn(II) complex (1) and Cu(II) complex (2) with isoeuxanthone. The interactions of them with calf thymus (ct DNA) have also been studied by absorption spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy and viscosity measurements. In addition, they were evaluated for their cytotoxic activities toward human esophageal cancer (ECA109) and human gastric cancer (SGC7901) cells by microculture tetrazolium (MTT) method. ExperimentalMaterials The ligand HL (isoeuxanthone, namely 1,6-dihydroxyxanthone) was prepared according to the literature 16) with some improvement. All the chemicals were reagent grade and were used without further purification. Calf thymus DNA (ct DNA) and ethidium bromide (EB) were obtained from Sigma Chemical Co. All the measurements involving the interactions of the two complexes with ct DNA were carried out in doubly distilled water buffer containing 5 mM Tris[Tris(hydroxymethyl)-aminomethane] and 50 mM NaCl, and adjusted to pH 7.1 with hydrochloric acid. UV-Vis spectrometer was employed to check a solution of ct DNA purity (A 260 : A 280 Ͼ1.80) and the concentration (eϭ6600 M Ϫ1 cm Ϫ1 at 260 nm) in the buffer. 17,18)Physical Measurements Elemental analyses were conducted using an Elementar Vario EL elemental analyzer. The metal contents of the complexes were determined by titration with EDTA (ethylenediamine tetraacetic acid). Infrared ...

Luminescent zinc salophen derivatives: cytotoxicity assessment and action mechanism studies

“…Such variations are indicative of a likely intercalation mode of the two complexes into ct double helix DNA, most likely similar to that obtained with ethidium bromide, EB (see below). 66 Nevertheless, the association constant between DNA and ethidium bromide is two orders of magnitude higher than the one calculated for our complexes showing that EB is a stronger intercalating agent.…”

Cytotoxicity towards human alimentary system carcinoma cells resulting from diverse copper(II) complexes

“…IC 50 values of 2 and 3 reach about 10 μM, lower than that of some previously reported analogous copper(II) complexes against these human alimentary system carcinoma cell lines [18][19][20][33][34][35][36], indicating that 2 and 3 have potent cytotoxicity.…”

“…Four human alimentary system carcinoma cell lines, SGC7901 (gastric tumor cell line), EC109 (esophagus tumor cell line), SMMC7721 (liver tumor cell line), and HT29 (colon tumor cell line), were utilized in our work. These cell lines were chosen to explore the potential selectivity of our copper(II) complexes towards different human alimentary system carcinoma cell lines and all have been previously used in studies with copper complexes that are cytotoxic [18][19][20][21]. IC 50 values indicated that 2 and 3 have promising cytotoxicity.…”

Advances in Copper Complexes as Anticancer Agents

“…The mononuclear Cu­(II) complex [Cu­( L 26a ) 2 ] (Figure b) promoted an intercalative interaction with CT-DNA with a calculated binding constant value of 2.5 × 10 4 M –1 . Complex 26a showed a moderate cytotoxic potency toward ECA109 (IC 50 = 20.8 μM) and SGC-7901 (IC 50 = 25.7 μM) cells . Insertion of a pendant piperidinyl-ethoxy group onto the isoeuxanthone moiety did not enhance the biological properties of the corresponding 26b complex (Figure b) …”