A Novel Synthetic Steroid of 2ß,3α,5α-Trihydroxy-androst-6-one Alleviates the Loss of Rat Retinal Ganglion Cells Caused by Acute Intraocular Hypertension via Inhibiting the Inflammatory Activation of Microglia.

Neuroinflammation has been well recognized as a key pathological event in acute glaucoma. The medical therapy of acute glaucoma mainly focuses on lowering intraocular pressure (IOP), while there are still scarce anti-inflammatory agents in the clinical treatment of acute glaucoma. Here we reported that ß,3α,5α-trihydroxy-androst-6-one (sterone), a novel synthetic polyhydric steroid, blocked neuroinflammation mediated by microglia/macrophages and alleviated the loss of retinal ganglion cells (RGCs) caused by acute intraocular hypertension (AIH). The results showed that sterone significantly inhibited the morphological changes, the up-regulation of inflammatory biomarker ionized calcium-binding adapter molecule 1 (Iba-1), and the mRNA increase of proinflammatory tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) induced by lipopolysaccharide (LPS) in BV2 microglia and RAW264.7 macrophages. Moreover, immunofluorescence and western blotting analysis revealed that sterone markedly abrogated the nuclear translocation and phosphorylation of nuclear factor-κB (NF-κB) p65 subunit. Furthermore, sterone significantly suppressed the inflammatory microglial activation and RGCs' reduction caused by retinal ischemia/reperfusion (I/R) injury in a rat AIH model. These results suggest sterone may be a potential candidate in the treatment of acute glaucoma caused by microglial activation-mediated neuroinflammatory injury.

Anticancer activity studies of a ruthenium(II) polypyridyl complex against human hepatocellular (BEL-7402) cells.

A Ru(II) polypyridyl complex [Ru(bpy)2(HMSPIP)](ClO4)2 (1) (bpy=2,2'-bipyridine, HMSPIP=2-(4-methylsulfonyl)phenyl-1H-imidazo[4,5-f][1,10] phenanthroline) was synthesized. The IC50 value of the complex against human hepatocellular cell BEL-7402 is 21.6±2.7 µM. The complex shows no cytotoxic activity toward human lung adenocarcinoma cell A549, human osteosarcoma cell MG-63 and human breast cancer cell SK-BR-3 cells. It is easily for complex 1 to be taken up by BEL-7402 cells. The complex can enhance the reactive oxygen species (ROS) levels and induce the decrease in the mitochondrial membrane potential. The complex inhibits the cell growth in BEL-7402 cells at G2/M phase. Complex 1 can regulate the expression of Bcl-2 family proteins. The results show that the complex induces apoptosis of BEL-7402 cells through a ROS-mediated mitochondrial dysfunction pathway.

Ruthenium(II) complexes: DNA-binding, cytotoxicity, apoptosis, cellular localization, cell cycle arrest, reactive oxygen species, mitochondrial membrane potential and western blot analysis.

The aim of our study was to investigate DNA-binding and cytotoxic activity of the four new Ru(II) polypyridyl complexes [Ru(dmb)2(HMHPIP)](ClO4)2 (1), [Ru(bpy)2(HMHPIP)](ClO4)2 (2), [Ru(phen)2(HMHPIP)](ClO4)2 (3) and [Ru(dmp)2(HMHPIP)](ClO4)2 (4). The complexes interact with DNA through intercalative mode and show relatively high cytotoxic activity against A549 cells, no cytotoxicity toward MG-63 cells. Complexes 1-4 can enhance the levels of ROS in A549 cells and induce the decrease of the mitochondrial membrane potential. These complexes inhibit the cell growth in A549 cells at G0/G1 or S phase. Complex 3 activated caspase 7, and down-regulated the expression of the anti-apoptotic protein Bcl-2. Complexes 1-4 induce apoptosis in A549 cells through ROS-mediated mitochondrial dysfunction pathway.

Synthesis, molecular structure, DNA-binding, cytotoxicity, apoptosis and antioxidant activity of compounds containing aryloxazole.

Three novel aryloxazole compounds 1-3 were synthesized and characterized. The crystal structures of compounds 2 and 3 show that N atom locates at ß-position and O atom at α-position in naphthalene cycle. The DNA binding constants for compounds 1-3 are 4.44 × 10(3), 5.31 × 10(3) and 2.64 × 10(3) 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.

Synthesis, characterization, DNA interaction, antioxidant and anticancer activity studies of ruthenium(II) polypyridyl complexes.

Two new Ru(II) polypyridyl complexes [Ru(phen)2(adppz)](ClO4)2 (1) and [Ru(dip)2(adppz)](ClO4)2 (2) have been synthesized and characterized. The DNA-binding constants were determined to be 6.54 ± 0.42 × 10(5) and 7.65 ± 0.20 × 10(5)M(-1) for complexes 1 and 2. DNA binding experiments indicated that complexes 1 and 2 interact with DNA through intercalative mode. Antioxidant activity shows that the complexes have significant hydroxyl radical scavenging activity. Cytotoxic activities suggest that the complex 2 exhibits higher cytotoxic activity against BEL-7402, MG-63 and SKBR-3 cells than complex 1 under identical conditions. Complexes 1 and 2 can induce apoptosis of BEl-7402 cells. We have identified several cellular mechanisms induced by 1 and 2 in BEL-7402 cells, including the level detection of ROS, activation of procaspase 3, caspase 7, the expression of antiapoptotic proteins Bcl-x, Bcl-2, proapoptotic proteins Bad, Bax, Bid and cell cycle arrest. Thus, complexes 1 and 2 inhibit growth of BEL-7402 cells through induction of apoptotic cell death, enhancement of ROS levels and S-phase and G0/G1 cell cycle arrest. Further investigations have shown that complex 2 induces apoptosis by regulating the expression of Bcl-2 family proteins.

Cytotoxicity, apoptosis, cell cycle arrest, reactive oxygen species, mitochondrial membrane potential, and Western blotting analysis of ruthenium(II) complexes.

Three new ruthenium(II) complexes-[Ru(bpy)2(adppz)](ClO4)2, [Ru(dmb)2(adppz)](ClO4)2, and [Ru(dmp)2(adppz)](ClO4)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)](ClO4)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)](ClO4)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 G0/G1 phase. Western blotting analysis shows that [Ru(dmp)2(adppz)](ClO4)2 induces apoptosis in BEL-7402 cells through activation of caspase 3, caspase 7, and procaspase 7 and ROS-mediated mitochondrial dysfunction pathways.

DNA-binding, photocleavage, cytotoxicity in vitro, apoptosis and cell cycle arrest studies of symmetric ruthenium(II) complexes.

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) × 10(5) and 7.42 (±0.53) × 10(5) 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.

Cytotoxicity, cell cycle arrest, antioxidant activity and interaction of dibenzoxanthenes derivatives with DNA.

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 5.05×10(4), 2.13×10(3), 5.10×10(4), and 3.03×10(3) 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).