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Phytochemical investigation on the stems of Schisandra glaucescens resulted into the isolation of three new lanostane triterpenoids, 12-hydroxyschiglausin B (1), 12-hydroxykadsuphilactone B (2), and 20R-hydroxyschinalactone C (3). Structural elucidation of all the compounds was accomplished by spectral methods. The isolated compounds were tested in vitro for cytotoxic activities. As a result, triterpenoids 1 and 2 showed cytotoxic activities for all six tested tumor cell lines with IC50 values less than 15 μM. [ABSTRACT FROM AUTHOR]

Complexes [Zn(L)2(H2O)] ( 1), [Mn(L)2(CH3OH)2] ( 2), and [Fe(L)2(CH3OH)Cl] ( 3) (H-L = 6-hydroxyloxoisoaporphine) were synthesized and characterized. Complex 1 is a five-coordinate distorted tetragonal pyramid, whereas complexes 2 and 3 are six-coordinate distorted octahedral structures. Complexes 1- 3 exhibited selective cytotoxicity against MGC80-3, Hep-G2, BEL-7404, and T-24 cells, with IC50 values in the range of 8.19-15.98 µ m, and low cytotoxicity to HL-7702 cells. T-24 was the tumor cell most sensitive to complexes 1- 3. Complexes 1- 3 induced T-24 cell arrest in the G1 and G2/M phases, which led to the upregulation of p27, CDK2, p53, and p21, and downregulation of Cyclin E, Chk1, CDC25A, and Chk2. Complexes 1- 3 triggered apoptosis in T-24 cells by a mitochondrial-dysfunction pathway. The interaction of complexes 1- 3 with DNA occurs most likely by means of an intercalation and cleavage mode. [ABSTRACT FROM AUTHOR]

A series of novel 1,2,3-triazole-linked isosteviol derivatives were designed and synthesized via Huisgen-click reaction. Their cytotoxicities in vitro against HCT-116 and JEKO-1 cells were screened. The preliminary bioassays indicated that most of the title compounds exhibited noteworthy cytotoxic activities. Particularly, the compound 10b revealed the most potent inhibitory activities against HCT-116 cells with IC 50 value of 2.987 ± 0.098 μM, which was better than that (3.906 ± 0.261 μM) of positive control cisplatin. On the basis of these bioactivity data, hologram quantitative structure–activity relationship (HQSAR) was performed, and a statistically reliable model with good predictive power ( r 2 = 0.848, q 2 = 0.544 and R 2 pred = 0.982) was achieved. Additionally, the contribution maps derived from the optimal model explained the individual atomic contributions to the activity for each molecule. [ABSTRACT FROM AUTHOR]

Abstract: Two new dimeric diarylheptanoids, named Alpinin C (1) and D (2), a new natural product of diarylheptanoid (3) along with three known diarylheptanoids (4–6) were isolated from the rhizomes of Alpinia officinarum Hance. Their structures were elucidated based on extensive spectroscopic analyses (1D and 2D NMR, HRTOFMS, IR). The isolated compounds were evaluated for their cytotoxicity against human tumor cell lines HepG2, MCF-7, T98G and B16-F10. Compound 1 showed selective cytotoxicity against cell lines of MCF-7 and T98G, while compound 6 showed significant cytotoxicity to the all tested tumor cell lines with IC50 in the range from 8.46 to 22.68μmol/L. [Copyright &y& Elsevier]

Abstract: [Zn2(ClQ)4(CH3OH)2] (1), [Zn(BrQ)2(H2O)2] (2), [Zn2(ClIQ)4] (3) and [Cu(BrQ)2] (4) (H-ClQ = 5,7-dichloro-8-hydroxylquinoline, H-BrQ = 5,7-dibromo-8-hydroxylquinoline, and H-ClIQ = 5-chloro-7-iodo-8-hydroxylquinoline) were synthesized. Compounds 1–4 showed high anti-proliferative cytotoxicities against BEL-7404, SK-OV-3, NCI-H460 tumor cells, and HL-7702 normal cells in vitro, with IC50 values in the 1.4 nM to 32.13 μM range. Compounds 2–4 exhibited significantly enhanced cytotoxicity against BEL-7404 cell line, comparing with free 5,7-dihalo-8-quinolinol. Western blotting analysis showed that 2, 3 depleted mutant p53 protein in MDA-MB-231, and compound 2 decreased the ratio of Bcl-2/Bax in NCI-H460 significantly. The binding abilities of 1–4 to DNA were stronger than that of free quinolinol ligand. Intercalation is the probable binding mode for the complexes and free quinolinol ligands with DNA. [Copyright &y& Elsevier]

Chemical examination of the ethanol extract of rhizomes of Iris tectorum led to the isolation and characterization of three new lignans, (7 R ,7′ R ,8 S ,8′ S )-5′-methoxy-neo-olivil (1a), (7 S ,7′ S ,8 R ,8′ R ) -5′-methoxy-neo-olivil (1b), (7 S ,7′ R ,8 S ,8′ S )-neo-olivil (2a), (7 R ,7′ S ,8 R ,8′ R )-neo-olivil (2b), (7 R ,7′ R ,8 S ,8′ S ,7′′ S ,8′′ S )- threo -neo-olivil-4′-O-8-guaiacylglycerol ether (3), together with six known ones (4–9). Among them, compounds 1 and 2 were found to be racemic mixtures, respectively, which were verified by chiral HPLC analysis, compound 3 was a new sesquineolignan. The structures were elucidated on the basis of extensive spectroscopic analysis. To our knowledge, this is the first report of lignan constituents isolated from I. tectorum . All compounds were evaluated for their cytotoxicity against five human tumor cell lines and none of them displayed significant toxicity in tested cell lines at a concentration of 10 μM. [ABSTRACT FROM AUTHOR]

Five new phorbol esters, (four phorbol diesters, 1 – 4 , and one 4-deoxy-4α-phorbol diester, 5 ), as well as four known phorbol esters analogues ( 6 – 9 ) were isolated and identified from the branches and leaves of Croton tiglium . Their structures were elucidated mainly by extensive NMR spectroscopic, and mass spectrometric analysis. Among them, compound ( 1 ) was the first example of a naturally occurring phorbol ester with the 20-aldehyde group. Compounds 2 – 5 , and 7 – 9 showed potent cytotoxicity against the K562, A549, DU145, H1975, MCF-7, U937, SGC-7901, HL60, Hela, and MOLT-4 cell lines, with IC 50 values ranging from 1.0 to 43 μM, while none of the compounds exhibited cytotoxic effects on normal human cell lines 293T and LX-2, respectively. In addition, compound 3 exhibited moderate COX-1 and COX-2 inhibition, with IC 50 values of 0.14 and 8.5 μM, respectively. [ABSTRACT FROM AUTHOR]

Abstract: Three new copper(II) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline (PYP), i.e. [Cu2(PYP)2Cl4] (1), [Cu4(PYP)4(ClO4)2(H2O)2](ClO4)2·2H2O (2), and [Cu2(PYP)2Cl4] n (3), were synthesized and fully characterized. In comparison to free PYP, complexes 1–3 exhibited enhanced cytotoxicity against tested human tumor cell lines BEL-7404, SK-OV-3, A549, A375, MGC-803 and NCI-H460, with IC50 values ranging from 0.31 to 30.76 μM. Complexes 1–3 exhibited lower cytotoxicity to HL-7702 than them to cancer cells. Complex 1 induced apoptotic death of BEL-7404, which involved mitochondria in the process. Caspase-3 activation assay indicated that 1 could be an efficient activator of caspase-3. DNA binding studies by UV–vis, DNA-melting, competitive binding, CD, viscosity measurement and agarose gel electrophoresis, revealed that intercalation might be the most likely binding mode of 1 with DNA. [Copyright &y& Elsevier]

Three cerium complexes: [Ce(ClQ)4] (1) (H-ClQ = 5,7-dichloro-8-hydroxylquinoline), [Ce(ClIQ)4]·CH2Cl2·0.5H2O (2) (H-ClIQ = 5-chloro-7-iodo-8-hydroxylquinoline) and [Ce2(BrQ)4(H-BrQ)(H2O)3Cl2]·1.5H2O (3) (H-BrQ = 5,7-dibromo-8-hydroxylquinoline) were synthesized. The structures of 1 and 2 are mononuclear whereas 3 has a binuclear structure. Compared with the H-ClQ, H-ClIQ and H-BrQ, complexes 1–3 exhibited significantly higher cytotoxicity (IC50 = 0.09–5.23 μM) to SK-OV-3 and BEL-7404, 1 and 2 exhibited higher cytotoxicity to NCI-H460. Most the complexes and ligands exhibited higher cytotoxicity than cisplatin. Complexes 1–3 are much more sensitive to SK-OV-3 than to human normal liver cell HL-7702. Their antitumor activities were achieved through cell apoptosis and arrest at G0/G1-phase. Studies on the binding properties of 1–3 to DNA indicate that intercalation is the most probable binding mode. [ABSTRACT FROM AUTHOR]

Abstract: Six new platinum(II) complexes with mono-aminophosphonate ester were synthesized and characterized by elemental analysis, 1H NMR, ESI-MS as well as single crystal X-ray diffraction analysis. They are mononuclear structures. In all the crystal structures of complexes 1–6, the platinum centre adopts an approximately square-planar geometry, which were found to possess excellent solubility in both organic solvents and water and exhibit considerable cytotoxicity against MG-63, SK-OV-3 and HepG2 cell lines, but low cytotoxicity towards normal human liver cell HL-7702. In contrast to cisplatin, their antitumour activities are achieved through the induction of cell apoptosis by G1 cell-cycle arrest. [Copyright &y& Elsevier]

[Pt(Q) 2 ] ( 1 ) and [Pt(MQ) 2 ] ( 2 ) exhibited enhanced cytotoxicity against BEL-7404, Hep-G2, NCI–H460, T-24, A549 tumor cells but low cytotoxicity on normal HL-7702 cells. 1 and 2 could cause the cell cycle arrest in G2 and S phase, respectively. While pifithrin-α, a specific p53 inhibitor, induced cell cycle arrest in G1 phase. Although 1 , 2 and pifithrin-α caused serious inhibition on p53, 1 and 2 significantly cause the loss of mitochondrial membrane potential and increase of the reactive oxygen species level, cytochrome c , apaf-1 and caspase-3/9 ratio in BEL-7404 cells. 1 and 2 may trigger the cell apoptosis through a mitochondrial dysfunction pathway whereas pifithrin-α does not. The interactions of 1 and 2 with DNA are most probably via an intercalation. [ABSTRACT FROM AUTHOR]

Abstract: Three mononuclear silver(I) complexes with 8-hydroxyquinoline, 8-hydroxy-2-methylquinoline and 5-chloro-8-quinolinol were synthesized and characterized by elemental analysis, NMR, ESI-MS as well as single crystal X-ray diffraction analysis. All the structures of complexes 1–3 with the silver center adopting an approximately four-coordinated distorted tetragonal pyramid geometry were found to exhibit selective cytotoxicity against HepG2, NCI-H460, BEL-7404 and HeLa cell lines with IC50 values generally in the micromolar range (1.7–14.6μM), but low cytotoxicity towards normal human liver cell HL-7702. A combination of flow cytometric analysis and molecular probe observation indicated that complexes 1–3 could induce HepG2 cell apoptosis. Molecular mechanism studies suggested that complexes 1–3-induced apoptosis is mediated through the intrinsic apoptotic pathway with changes in mitochondrial membrane potential by finally activating effector caspase-3/9 to trigger cell apoptosis. Further studies revealed that complexes 1 and 2 caused cell cycle arrest at S phase, while complex 3 induced G1 cell cycle arrest in HepG2 cells. Taken together, these results suggest that complexes 1–3 may be potential candidates for cancer therapy. [Copyright &y& Elsevier]

Abstract: Three tin(IV) complexes [Sn(ClQ)2Cl2] (1), [Sn(BrQ)2Cl2] (2) and [Sn(ClIQ)2Cl2] (3) were prepared (H-ClQ = 5,7-dichloro-8-hydroxylquinoline, H-BrQ = 5,7-dibromo-8-hydroxylquinoline, H-ClIQ = 5-chloro-7-iodo-8-hydroxylquinoline) and their in vitro cytotoxicities against BEL7404, SKOV-3, NCI-H460, HL-7702 cell lines were evaluated. The complexes showed high anti-proliferative activity toward the tested cell lines with IC50 values ranging from 20 nM to 5.11 μM. Compared with 5,7-dihalo-8-quinolinol, most complexes exhibited significantly enhanced cytotoxicity (except 2 against SKOV-3 and NCI-H460). They also displayed some selective cytotoxicity favoring the tested tumor cells over the normal human liver HL-7702 cells. Compared with their quinolinol ligands, complexes 1–3 bind more strongly with DNA. Intercalation is the most probable binding mode for both the complexes and their quinolinol ligands. [Copyright &y& Elsevier]