We found that complex 1 induced MGC80-3 cell apoptosis via a mitochondrial dysfunction pathway, which was mediated by , ROS, and intracellular Ca2+

Human Leukocyte Elastase 0 Comments

We found that complex 1 induced MGC80-3 cell apoptosis via a mitochondrial dysfunction pathway, which was mediated by , ROS, and intracellular Ca2+. activities include mainly halogenated derivatives [22,23], diperazino and alkyno derivatives [24,25], nitro derivatives [26,27,28], carboxylic and carboxamido derivatives [29,30,31], amino and imino derivatives [32,33], sulfoxine and sulfonamide derivatives [34,35,36], Bis- and poly-HQs [37,38], HQ bioconjugates [39,40,41], and other HQ derivatives [42]. In addition, it is well known that quinolinylhydrazones show various important biological activities and the quinoline ring plays an important role in the development of new anticancer agents [43,44,45,46,47]. For example, the quinolinylhydrazones exhibit significant cytotoxicity in comparison with similar reported systems and the apoptosis induction in MCF-7 cancer cells increased when it was coordinated with the gold nanoparticle surface [48]. Recently, the synthesis of 2-((2-(pyridin-2-yl)hydrazono)methyl)quinolin-8-ol (L) was reported [49]. The metal complexes of HQs show enhanced tumor cytotoxicity [50,51,52,53,54,55,56], including ruthenium [50,51], gold [52], platinum [53], copper [43,48,49], and vanadium [44] complexes. However, there are few reports on the synthesis and antitumor activity of Cu(II) and Ni(II) complexes. Chan et al. found that 8-hydroxy-2-quinolinecarbaldehyde (Scheme 1) showed the highest in vitro cytotoxicity against the human cancer cell lines, including MDA231, T-47D, Hs578t, SaoS2, K562, SKHep1, and Hep3B [42]. Therefore, as part of our continuing work on the synthesis, characterization and medicinal application of metal complexes with HQ [45,46,47], we report the synthesis and characterization of Cu(II) and Ni(II) complexes with 2-((2-(pyridin-2-yl)hydrazono)methyl)quinolin-8-ol (L) and the in vitro cytotoxicities against seven tumor cells and their antitumor mechanism. 2. Results 2.1. Synthesis As outlined in Scheme 2, complexes 1, 2 were synthesized by the reaction of L with CuCl22H2O and NiCl26H2O in hot methanol, respectively. They were satisfactorily characterized by mass spectrometry (MS), elemental analysis (EA), infrared spectroscopy (IR), and single-crystal X-ray diffraction analysis. The absorptions around 1550C1650 cm?1 of the IR (Figures S3CS5) were assigned to the imine bond stretching vibrations of L. The imine bonds of complexes 1 and 2 underwent a left-shift of 10C60 cm?1 upon coordination, indicating the participation of this group in coordination. The single-crystal structure analysis suggested that the Cu(II) complex was [Cu(L)Cl2]2 (1) and the Ni(II) complex was [Ni(L)Cl2]CH2Cl2 (2). 2.2. Crystal Structures of Complexes 1 and 2 The crystal data and refinement details of complexes 1 and 2 are summarized in Table S1 (Supporting Information), and the selected bond lengths and angles are listed in Tables S2 and S3. The crystal structures of complexes 1 and 2 are shown in Figure 1 and Figure 2. Complexes 1 Rabbit Polyclonal to NT and 2 have different coordination pattern. Complex 1 was a dinuclear L-Cu-Cl-(-Cl)2-Cu-Cl-L complex, and the Cu(II) ions were coordinated by three Cl and two N atoms from L in a distorted square pyramidal geometry. Open in a separate window Figure 1 The crystal structure of Cu(II) NECA complex 1. Open in a separate window Number 2 The crystal structure of complex 2. In complex 2, the central NiII used an approximately five-coordinated tetragonal pyramidal geometry. NECA 2.3. Stability in Answer Ligand L, complexes 1 and 2 were tested for his or her stabilities in both dimethyl sulfoxide (DMSO) and Tris-HCl buffer answer (TBS) (TBS answer with pH at 7.35, containing 1% DMSO) by means of UV-Vis spectroscopy. The time-dependent (in the time NECA course of 0, 12, 24, 36 and 48 h) UV-Vis spectra of each complex dissolved in TBS answer are demonstrated in Number S1. There were no obvious changes in the NECA spectral characteristics and the maximum absorptions for ligand L, complexes 1 and 2 over the time program. In addition, the stabilities of L, complexes 1 and 2 were monitored by high performance liquid chromatography (HPLC) recognized at 245 nm, and no significant switch was observed for these three compounds in TBS at 0, 24, and 48 h (Number S2). Combining the ESI-MS data, the results suggested that complex 2 was stable in TBS answer, and complexes 1 was stable in TBS answer as mononuclear varieties because it was dissociated in water answer and Tris-HCl buffer (see the results of Number S9). 2.4. In Vitro Cytotoxicity The in vitro cytotoxicities of L, complexes 1 and 2 were evaluated by MTT assay in seven human being tumor cell lines Hep-G2, SK-OV-3, MGC80-3, HeLa, T-24, BEL-7402, and NCI-H460 and one normal liver cell collection HL-7702. Each compound was prepared as 2.0 mM.