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The DNA-binding, photocleavage, and antitumor activity of three free base pyridyl corroles 1, 2, and 3 have been investigated. The binding affinity toward CT-DNA decreases with increasing number of pentafluorophenyl, whereas the photocleavage activity toward pBR322 DNA becomes more efficient. Singlet oxygen was demonstrated as active species responsible for DNA cleavage. These corroles exhibited high cytotoxicity against three tested cancer cells (Hela, HapG2, and A549) and the cytotoxicity could be further enhanced under irradiation. Intracellular reactive oxygen species level was also monitored using HeLa Cells upon the combined treatment of corroles and light. These corroles could be absorbed by HeLa cells at low concentration. They can induce the decrease of mitochondrial membrane potential and apoptosis of tumor cells under irradiation. [ABSTRACT FROM AUTHOR]

Two dibenzoxanthene isomers 3 and 4 were synthesized and characterized. The crystal structures of the two compounds were solved by single-crystal X-ray diffraction. Binding of two compounds with calf thymus DNA (CT DNA) and BSA (bovine serum albumin) has been thoroughly investigated by UV-Vis and fluorescence spectroscopy. The DNA-binding constants were determined to be 2.51 (± 0.09) × 10(3) for compound 3 and 4.55 (± 0.10) × 10(3) for compound 4. Two compounds can cleave pBR322 DNA upon irradiation. Significant nuclear damages of BEL-7402 cells were observed with compound treatment in a comet assay. The cytotoxicity in vitro was investigated by MTT method. These compounds have been found to induce nuclear condensation and fragmentation in BEL-7402 cells. The two compounds can enhance intracellular reactive oxygen species and decrease the mitochondrial membrane potential. The compounds activated caspase-3 and caspase-7, down-regulated the expression levels of anti-apoptotic protein Bcl-2, and up-regulated the expression levels of pro-apoptotic protein Bax. These compounds induce apoptosis of BEL-7402 cells through an ROS-mediated mitochondrial dysfunction pathway. [ABSTRACT FROM AUTHOR]

Two new Ru(II) complexes, [Ru(bpy)2(FAMP)](ClO4)21 and 2, are synthesized and characterized by elemental analysis, electrospray mass spectrometry, and 1H nuclear magnetic resonance. The in vitro cytotoxicities and apoptosis-inducing properties of these complexes are extensively studied. Complexes 1 and 2 exhibit potent antiproliferative activities against a panel of human cancer cell lines. The cell cycle analysis shows that complexes 1 and 2 exhibit effective cell growth inhibition by triggering G0/G1 phase arrest and inducing apoptosis by mitochondrial dysfunction. The in vitro DNA binding properties of the two complexes are investigated by different spectrophotometric methods and viscosity measurements. [ABSTRACT FROM AUTHOR]

Three new ruthenium(II) complexes—[Ru(bpy) 2(adppz)](ClO 4) 2, [Ru(dmb) 2(adppz)](ClO 4) 2, and [Ru(dmp) 2(adppz)](ClO 4) 2 (bpy is 2,2′-bipyridine, adppz is 7-aminodipyrido[3,2- a:2′,3′- c]phenazine, dmb is 4,4′-dimethyl-2,2′-bipyridine, and dmp is 2,9-dimethyl-1,10-phenanthroline)—were synthesized. [Ru(dmp) 2(adppz)](ClO 4) 2 exhibits higher cytotoxicity than cisplatin toward A549, MG-63, and SKBR-3 cells. The apoptosis and cellular uptake were studied by fluorescence microscopy. [Ru(dmp) 2(adppz)](ClO 4) 2 enhances the level of reactive oxygen species (ROS) and decreases the mitochondrial membrane potential. These complexes induce cell cycle arrest in S phase in BEL-7402 cells, and inhibit the antiproliferation of SKBR-3 cells at G 0/G 1 phase. Western blotting analysis shows that [Ru(dmp) 2(adppz)](ClO 4) 2 induces apoptosis in BEL-7402 cells through activation of caspase 3, caspase 7, and procaspase 7 and ROS-mediated mitochondrial dysfunction pathways. Graphical abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Two new ruthenium(II) polypyridyl complexes, [Ru(dmb)2(DNPIP)](ClO4)2 (1) (DNPIP = 2-(2,4-dinitrophenyl)imidazo[4,5-f][1,10]phenanthroline, dmb = 4,4′-dimethyl-2,2′-bipyridine) and [Ru(dmb)2(DAPIP)](ClO4)2 (2) (DAPIP = 2-(2,4-diaminophenyl)imidazo[4,5f][1,10]phenanthroline), were synthesized and characterized. The DNA-binding behaviors of these complexes have been studied by UV-Vis absorption titration, viscosity measurements, and photocleavage. The DNA-binding constants are 7.39 (±0.16) × 104 (s = 2.68) and 2.73 (±0.16) × 104 (mol L−1)−1 (s = 0.64) for 1 and 2, respectively. Their evaluation as cytotoxic agents on different cancer cell lines was investigated with IC50 values of 59.5, 51.3, and 70.3 µmol L−1 for 1, >100, 87.9, and 77.9 µmol L−1 for 2 against BEL-7402, HepG-2, and MCF-7 cells, respectively. Complex 1 is more active than 2 against selected cancer cell lines. The apoptosis induced by these complexes was studied. Cellular uptake showed that these complexes could enter into the cytoplasm and accumulate in the nuclei. The cell cycle arrest and antioxidant activity against hydroxyl radicals were also investigated. [ABSTRACT FROM PUBLISHER]

In this study, we report the DNA interaction and cytotoxicity of four dibenzoxanthene compounds 1-4. The binding behaviors of these compounds to calf thymus DNA were studied by absorption titration, viscosity measurements. The DNA binding constants of compounds 1, 2, 3, and 4 are 5.05×104, 2.13×103, 5.10×104, and 3.03×103 M−1, respectively. The lipophilicity of the compounds was determined by the shake flask method. The cytotoxicity of these compounds has been assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. These compounds exhibit high activity against BEL-7402, Hela, MG-63, and SKBR-3 cells. The cell cycle arrest was analyzed by flow cytometry. These compounds inhibit S phase of BEL-7402 and SKBR-3 cells. The experiments on antioxidant activity show that these compounds exhibit good antioxidant activity against hydroxyl radical (•OH). Four compounds of this family bind DNA, are cytotoxic in an in vitro assay of mitochondrial potential, show antioxidant activity, and cause damage during S phase in cell lines. [ABSTRACT FROM AUTHOR]

Two new ruthenium(II) polypyridyl complexes [Ru(dmb)2(HECIP)](ClO4)2 (1) (HECIP = N-ethyl-4-[(1,10)-phenanthroline(5,6-f)imidazol-2-yl]carbazole, dmb = 4,4’-dimethyl-2,2’-bipyridine) and [Ru(dmp)2(HECIP)](ClO4)2 (2) (dmp = 2,9-dimethyl-1,10-phenanthroline) have been synthesized and characterized. The DNA-binding behaviors of the two complexes were investigated by absorption spectra, viscosity measurements, and photoactivated cleavage. The DNA-binding constants for complexes 1 and 2 were determined to be 8.03 (± 0.12) × 104 M−1 (s = 1.62) and 2.97 (± 0.15) × 104 M−1 (s = 1.82), respectively. The results suggest that these complexes interact with DNA through intercalative mode. The photocleavage of pBR322 DNA by Ru(II) complexes was investigated. The cytotoxicity of complexes 1 and 2 has been evaluated by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)] method. Complex 1 shows higher anticancer potency than 2 against the four tumor cell lines. Apoptosis and cellular uptake were investigated. The antioxidant activities of the ligand and these complexes were also performed. [ABSTRACT FROM AUTHOR]

Two new ruthenium(II) complexes, [Ru(phen)2(DNPIP)](ClO4)2 (1) and [Ru(phen)2(DAPIP)](ClO4)2 (2), were synthesized and characterized. The DNA-binding properties of these complexes were investigated using UV/vis absorption titration, viscosity measurements, thermal denaturation, and photoactivated cleavage. The DNA binding constants for complexes 1 and 2 are 2.63 ± 0.25 × 105 M−1 ( s = 2.45) and 1.51 ± 0.18 × 105 M−1 ( s = 1.34). The results indicated that these complexes interacted with DNA through the intercalative mode. The cytotoxicity in vitro of complexes 1 and 2 were assessed against BEL-7402, HepG-2, and MCF-7 cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was studied with the acridine orange/ethidium bromide staining method. The antiproliferative mechanism was explored with flow cytometry. Cellular uptake studies showed that complexes 1 and 2 can enter into the cytoplasm and accumulate in the nuclei. Cell cycle arrest and antioxidant activity were also investigated. [ABSTRACT FROM AUTHOR]

Abstract: Ruthenium(II) polypyridyl complexes [Ru(phen)2(APIP)](ClO4)2 1 and [Ru(phen)2(HAPIP)](ClO4)2 2 have been synthesized and characterized. The DNA-binding behaviors were investigated by electronic absorption titration, luminescence spectra, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants K b for complexes 1 and 2 were determined to be 3.38 (±0.42) × 105 M−1 (s = 1.48) and 3.93 (±0.60) × 105 M−1 (s = 3.14), respectively. The studies on the photocleavage demonstrated that the effects of cleavage are concentration-dependent. The results showed that complexes 1 and 2 interact with CT-DNA by intercalative mode. The cytotoxicity of complexes 1 and 2 has been evaluated by MTT method. The apoptosis assay was carried out with acridine orange/ethidium bromide (AO/EB) staining methods. The cellular uptake showed that complexes can enter into the cytoplasm and accumulate in the nuclei. The antioxidant activity studies suggested that the ligands and complexes may be potential drugs to eliminate the radical. [Copyright &y& Elsevier]

Abstract: Two new ligands maip (1a), paip (1b) with their ruthenium (II) complexes [Ru(bpy)2(maip)](ClO4)2 (2a) and [Ru(bpy)2(paip)](ClO4)2 (2b) have been synthesized and characterized. The results show that complexes 2a and 2b interact with DNA through intercalative mode. The cytotoxicity of these compounds has been evaluated by MTT assay. The experiments on antioxidant activity show that these compounds exhibit good antioxidant activity against hydroxyl radical (OHmple-para> [Copyright &y& Elsevier]

Abstract: Two new ruthenium(II) polypyridyl complexes [Ru(dmb)2(Fpp)](ClO4)2 1 (Fpp=2-(3′,3′-difluoro-3,4-methylenedioxyphenyl)imidazo[4,5-f][1,10]phenanthroline, dmb=4,4′-dimethyl-2,2′-bipyridine) and [Ru(bpy)2(Fpp)](ClO4)2 2 (bpy=2,2′-bipyridine) have been synthesized and characterized by elemental analysis, FAB-MS, ES-MS, IR, 1H NMR and 13C NMR. The DNA-binding behaviors of these complexes were investigated by absorption spectroscopic titration, viscosity measurements, thermal denaturation and photocleavage. The mechanism studies of photocleavage reveal that singlet oxygen (1O2) and superoxide anion radical (O2 −) may play an important role in the photocleavage. The cytotoxicity of complexes 1 and 2 have been evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. [Copyright &y& Elsevier]

Graphical abstract A new iridium(III) complex was synthesized and characterization. The cytotoxic activity in vitro, apoptosis, comet assay, lysosomal membrane permeabilization, cell cycle arrest, mitochondrial membrane potential and the expression of Bcl-2 family proteins were investigated. Abstract A new iridium(III) polypyridyl complex [Ir(ppy) 2 (DPBD)](PF 6) (ppy = 2-phenylpyridine, DPBD = 4-(dipyrido[3,2- a :2′,3′- c ]phenazin-11-yl)benzene-1,2-diamine, Ir-1) was synthesized and characterized by element analysis, ESI-MS, IR, 1H NMR and 13C NMR. The cytotoxicity in vitro of the complex against cancer BEL-7402, A549, Eca-109 and normal LO2 cells was evaluated by 3-(4,5-dimethylthiazole)-2,5-diphenyltetraazolium bromide (MTT) method. The IC 50 values of the complex toward BEL-7402, A549 and Eca-109 are 13.8 ± 0.7, 14.5 ± 0.6 and 15.2 ± 2.4 µM, respectively. The apoptosis was studied with acridine orange (AO) and ethidium bromide (EB) staining method and comet assay. The reactive oxygen species including superoxide anion and NO, the location of the complex at lysosomes, lysosomal membrane permeabilization, location of the complex at mitochondria and the change of mitochondrial membrane potential were assayed under a fluorescent microscope. The complex can enhance the intracellular Ca2+ levels and induce a release of cytochrome c. In addition, the complex can cause autophagy and upregulate the expression of LC-3 and Beclin-1 proteins. The complex inhibits the cell growth at S phase. The effects of the complex on the expression of caspase 3 and Bcl-2 family proteins were explored. The results show that the complex induces apoptosis in BEL-7402 cells through lysosome–mitochondrial dysfunction pathway, which was accompanied by the regulation of Bcl-2 family proteins. [ABSTRACT FROM AUTHOR]

Four new ruthenium(II) polypyridyl complexes [Ru(dmb) 2 (DQTT)](ClO 4 ) 2 ( 1 ) (DQTT = 12-(1,4-dihydroquinoxalin-6-yl)-4,5,9,14-tetraazabenzo[b]triphenylene, dmb = 4,4′-dimethyl-2,2′-bipyridine), [Ru(bpy) 2 (DQTT)](ClO 4 ) 2 ( 2 ) (bpy = 2,2′-bipyridine), [Ru(phen) 2 (DQTT)](ClO 4 ) 2 ( 3 ) (phen = 1,10-phenanthroline) and [Ru(dmp) 2 (DQTT)](ClO 4 ) 2 ( 4 ) (dmp = 2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized by elemental analysis, ESI-MS, 1 H NMR and 13 C NMR. The cytotoxic activity in vitro of the complexes was evaluated against human BEL-7402, A549, HeLa, HepG-2 and MG-63 cancer cell lines by MTT (3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide) method. The IC 50 values of complexes 1 – 4 against BEL-7402 cells are 31.8 ± 1.0, 35.8 ± 1.6, 29.0 ± 0.8 and 25.0 ± 0.9 μM, respectively. The morphological apoptosis was investigated with AO/EB (acridine orange/ethidium bromide) and Hoechst 33258 staining methods. The DNA damage was assayed by comet assay. The inhibition of cell migration was evaluated by the wound healing assay. The levels of ROS (reactive oxygen species) and the changes of mitochondrial membrane potential were studied under fluorescent microscope. The percentages in the cells of apoptotic and necrotic cells and the cell cycle arrest were determined by flow cytometry. The expression of Bcl-2 family proteins was investigated by western blot analysis. The results show that the complexes induce BEL-7402 cells apoptosis through a ROS-mediated mitochondrial dysfunction pathway, which was accompanied by regulation of the expression of Bcl-2 family proteins. [ABSTRACT FROM AUTHOR]

A new ligand Adbdp and its four ruthenium(II) polypyridyl complexes [Ru(N-N) 2 (Adbdp)](ClO 4 ) 2 [N-N = dmb: 4,4′-dimethyl-2,2′-bipyridine 1 , bpy: 2,2′-bipyridine 2 , phen: 1,10-phenanthroline 3 and dmp: 2,9-dimethyl-1,10-phenanthroline 4 , Adbdp = acenaphtheno[2,3-b]-1,4-diazabenzo[i]dipyrido[3,2- a :2′,3′- c ]phenazine] were synthesized and characterized by elemental analysis, ESI-MS and 1 H NMR. The cytotoxicity in vitro of the complexes against BEL-7402, HeLa, MG-63 and A549 cells was studied by MTT method. The IC 50 values are 24.2 ± 1.9, 11.5 ± 3.6, 3.4 ± 0.3 and 9.7 ± 0.5 μM for complexes 1 , 2 , 3 and 4 toward A549 cells, respectively. The apoptosis was assayed with AO/EB and Hoechst 33258 staining methods. The cellular uptake was investigated with DAPI-stained cell nuclei. The reactive oxygen species and mitochondrial membrane potential were performed under fluorescent microscope. The cell cycle distribution was studied by flow cytometry and the protein expression of Bcl-2 family proteins was analyzed by western blot. The results show that the complexes induce A549 cell apoptosis through a ROS-mediated mitochondrial dysfunction pathway. [ABSTRACT FROM AUTHOR]

Two Ru(II) polypyridyl complexes [Ru(phen) 2 (idpq)](ClO 4 ) 2 ( 1 ) and [Ru(dmp) 2 (idpq)](ClO 4 ) 2 ( 2 ) were synthesized and characterized. Cytotoxicity, apoptosis, cell cycle arrest, reactive oxygen species and mitochondrial membrane potential were assayed. The IC 50 values of complexes 1 and 2 toward HepG-2, A549, MG-63 and HeLa cell lines range from 15.1 ± 2.1 to 24.8 ± 2.4 μM. The complexes can effectively induce apoptosis and induce cell cycle arrest at G0/G1 phase by an increase of 4.88% for 1 and 6.64% for 2 at G0/G1 phase in HeLa cells. Complexes 1 and 2 can enter the cytoplasm and accumulate in the nuclei. The complexes can enhance the level of reactive oxygen species. The ratio of the red/green is 0.74 and 0.52 for complexes 1 and 2 , which suggests that the complexes induce a decrease of mitochondrial membrane potential. These complexes induce apoptosis in HeLa through ROS-mediated mitochondrial dysfunction pathway. [ABSTRACT FROM AUTHOR]

Three novel aryloxazole compounds 1–3 were synthesized and characterized. The crystal structures of compounds 2 and 3 show that N atom locates at β-position and O atom at α-position in naphthalene cycle. The DNA binding constants for compounds 1–3 are 4.44 × 103, 5.31 × 103 and 2.64 × 103 M−1, respectively. The viscosity measurements indicate that these compounds intercalate between the DNA base pairs. Upon irradiation, compounds 1–3 can effectively cleave pBR322 DNA. The cytotoxicity of the compounds against BEL-7402, A549, MG-63 and SKBR-3 were assayed by MTT method. The apoptosis and cell cycle arrest were investigated towards A549 cells. The antioxidant activities of the compounds against hydroxyl radicals were also explored. [ABSTRACT FROM AUTHOR]

Highlights: [•] Two new ruthenium (II) complexes [Ru(phen)2(adppz)](ClO4)2 and [Ru(dip)2(adppz)](ClO4)2 were synthesized. [•] The DNA-binding behaviors were studies by absorption titration, luminescence spectra and viscosity measurements. [•] The cytotoxicity of these complexes was assayed by MTT method. [•] The apoptosis was investigated by AO/EB, Hoechst 33258 staining method and flow cytometry. [•] The cellular uptake, ROS, cell cycle arrest and western blotting analysis were investigated. [ABSTRACT FROM AUTHOR]

Highlights: [•] Two ruthenium complexes [Ru(dmp)2(NHPIP)](ClO4)2 Ru-1 and [Ru(dmp)2(AHPIP)](ClO4)2 Ru-2 were synthesized and characterized. [•] The cytotoxicity in vitro of Ru-1 and Ru-2 against four tumor cell lines was investigated. [•] The apoptosis in BEL-7402 cells induced by Ru-1 and Ru-2 was investigated by fluorescence microcopy and flow cytometry. [•] The cell cycle arrest was studied by flow cytometry. [•] The ROS and the change of mitochondrial membrane potential were detected. [ABSTRACT FROM AUTHOR]

Two novel ruthenium(II) complexes [Ru(dmb)2(addppn)](ClO4)2 (1) and [Ru(bpy)2(addppn)](ClO4)2 (2) were synthesized. The DNA-binding constants of complexes 1 and 2 were determined to be 4.78 (±0.49) × 105 and 7.42 (±0.53) × 105 M−1. The results indicate that complexes 1 and 2 interact with CT DNA through intercalative mode. The cytotoxicity in vitro of the complexes toward BEL-7402, HeLa, MG-63 and SKBR-3 cells was assessed by MTT assay. The apoptosis was carried out with Hoechst 33258 staining method and flow cytometry. The cellular uptake was observed under fluorescence microscope. The cell cycle arrest shows that the antiproliferative mechanism induced by complexes 1 and 2 on BEL-7402 cells is G0/G1 phase arrest. [ABSTRACT FROM AUTHOR]