Synthesis,characterization, and biological activity of new mixed ammine/amine platinum(IV) complexes

A series of mixed ammine/amine platinum(IV) complexes with lipophilic ligands in their axial positions were designed, synthesized, and spectrally characterized. In vitro cytotoxicity evaluation of these complexes and their lead compounds have been carried out against A549, SMMC-7721, MCF-7, and SW480 human cancer cell lines. The introduction of carboxylate ions as leaving group can improve the aqueous solubility and stability of the platinum(II) complexes. The carboxylato ligands and chloride ligands in the axial position markedly increased the lipophilicity and cytotoxicity of compounds C4 and C5. Particularly, compound C5 showed two to eight times higher cytotoxicity than cisplatin and satraplatin against selected cell lines. For its oral activity and no cross-resistance potentiality, C5 is expected to be an antitumor platinum drug candidate. This novel class of platinum compounds represents a valuable lead in the development of new-generation agents capable of demonstrating cytotoxicity superior to that of the clinically established cisplatin.     

Novel Perbutyrylated Glucose Derivatives of (–)-Epigallocatechin-3-Gallate Inhibit Cancer Cells Proliferation by Decreasing Phosphorylation of the EGFR: Synthesis,Cytotoxicity, and Molecular Docking

Lung cancer is one of the most commonly occurring cancer mortality worldwide. The epidermal growth factor receptor (EGFR) plays an important role in cellular functions and has become the new promising target. Natural products and their derivatives with various structures, unique biological activities, and specific selectivity have served as lead compounds for EGFR. D-glucose and EGCG were used as starting materials. A series of glucoside derivatives of EGCG (7–12) were synthesized and evaluated for their in vitro anticancer activity against five human cancer cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW480. In addition, we investigated the structure-activity relationship and physicochemical property–activity relationship of EGCG derivatives. Compounds 11 and 12 showed better growth inhibition than others in four cancer cell lines (HL-60, SMMC-7721, A-549, and MCF), with IC₅₀ values in the range of 22.90–37.87 μM. Compounds 11 and 12 decreased phosphorylation of EGFR and downstream signaling protein, which also have more hydrophobic interactions than EGCG by docking study. The most active compounds 11 and 12, both having perbutyrylated glucose residue, we found that perbutyrylation of the glucose residue leads to increased cytotoxic activity and suggested that their potential as anticancer agents for further development.     

胡椒基咪唑盐类化合物的合成及生物活性研究

从胡椒酸出发,通过还原、甲磺酸酯化、偶联和成盐四步反应合成了一系列新型的胡椒基咪唑盐类化合物,其结构经¹HNMR, ¹³CNMR,HRMS以及X射线单晶衍射确定.对合成的新化合物进行了体外抗肿瘤细胞毒活性筛选,结果表明,1-((苯并[d][1,3]二氧杂环戊烯-5-基甲基)-3-(2-萘甲基))-5,6-二甲基-1H-苯并[d]咪唑-3-溴盐(30)具有显著的细胞毒活性,对HL-60、SMMC-7721、A-549、MCF-7和SW-480肿瘤细胞株的活性均优于顺铂(DDP),尤其对HL-60肿瘤细胞株表现出较好的选择性细胞毒活性,其IC₅₀值约为顺铂的7.2倍.进一步研究表明,化合物30具有诱导SMMC-7721细胞株在细胞周期G0/G1期阻滞和细胞凋亡的作用.     

A new tremulane sesquiterpenoid from the fungus Irpex lacteus

A new tremulane sesquiterpenoid, named irlactam A (1), was isolated from cultures of the fungus Irpex lacteus. The new structure was elucidated by spectroscopic data analysis. The compound was tested for its cytotoxicities on HL-60, SMMC-7721, A-549, MCF-7, and SW480 cells and for its inhibitory activity against isozymes of 11β-hydroxysteroid dehydrogenases (11β-HSD).     

Synthesis and Antitumor Activity of 1-Substituted 1,2,3-Triazole-Mollugin Derivatives

A new series of mollugin-1,2,3-triazole derivatives were synthesized using a copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction of corresponding O-propargylated mollugin with aryl azides. All the compounds were evaluated for their cytotoxicity on five human cancer cell lines (HL-60, A549, SMMC-7721, SW480, and MCF-7) using MTS assays. Among the synthesized series, most of them showed cytotoxicity and most of all, compounds 14 and 17 exhibited significant cytotoxicity of all five cancer cell lines.     

A new abietane diterpenoid from the roots of Tripterygium regelii

A new abietane diterpenoid, tripterregeline A (1), together with six known diterpenoids (2–7), were isolated from the roots of Tripterygium regelii. The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparison with data reported in the literature. All isolated compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1–7 showed significant inhibitory effects against various human cancer cell lines with IC₅₀ values ranging from 0.58 to 21.06 μM.     

Structurally diverse diterpenoids from Trigonostemon howii

Phytochemical investigation on the stems and leaves of Trigonostemon howii resulted in the isolation of a new abietane diterpenoid, trigohowimine A (1), along with seven known structurally diverse diterpenoids (2–8). The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparison with data reported in the literature. New compound 1 was evaluated for its cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480. Compound 1 showed significant inhibitory effects against various human cancer cell lines with IC₅₀ values ranging from 0.82 to 8.53 μM.     

Cytotoxic ent-kaurane diterpenoids from Isodon henryi

Five new ent-kaurane diterpenoids, isodonhenrins A-E (1-5), together with thirteen known ones were isolated from the aerial parts of Isodon henryi. Their structures were identified by means of extensive spectroscopic analysis, and the absolute configurations of 1 were determined by single-crystal X-ray diffraction. Most of the diterpenoids were evaluated for their cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cell lines. Compound 17 showed significant inhibitory effects on five cell lines, and compounds 6, 9, 10, 11, 12 and 16 exhibited selective activity.     

Synthesis and antitumor activity of camptothecin- 4β-triazolopodophyllotoxin conjugates

Abstract

Two new compounds (9 and 10) having a camptothecin (CPT) analog conjugated to the 4β-azido-4-deoxypodophyllotixin analog by untilizing the copper-catalyzed azide-alkyne cycloadditon (CuAAC) reaction, and were evaluated for their cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480) using the MTT (3-(4,5-dimethyl-thiahiazo-2-yl)-2,5-diphenyltetrazolium bromide) assay. Two novel conjugates shown weak cytotoxicity, compound 10 showed highly potent against HL-60 cell line tested, with IC₅₀ value 17.69?±?0.19?μM. This compound suggested its potential as anticancer agents for further development.

     

Bioactive furanocoumarins from the stems and leaves of Clausena hainanensis

A new furanocoumarin, clauhainanin A (1), together with seven known furanocoumarins (2–8), were isolated from the stems and leaves of Clausena hainanensis. The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with data reported in the literature. All known compounds (2–8) were isolated from C. hainanensis for the first time. All isolated compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1–8 exhibited significant inhibitory effects with IC₅₀ values ranging from 1.36 to 18.96 μM.     

Cobalt(II) complexes with thiosemicarbazone as potential antitumor agents: synthesis,crystal structures,DNA interactions,and cytotoxicity

Two cobalt(II) complexes [Co(QCT)₂]·Cl·1.5H₂O (1) (QCT = quinoline-2-carboxaldehyde thiosemicarbazone) and [Co(QCMT)(CH₃OH)Cl₂] (2) (QCMT = quinoline-2-carboxaldehyde N⁴-methyl-thiosemicarbazone) have been synthesized and structurally characterized. Complex 1 crystallizes in a triclinic system with space group P–1 and complex 2 crystallizes in a monoclinic system with space group P2(1)/n. In both complexes the cobalt(II) center is six coordinated with distorted octahedral geometry. The interactions of two complexes with CT-DNA were investigated by electronic absorption spectra, circular dichroism (CD) spectra and fluorescence spectra. Results suggest that the complexes bind to DNA via groove binding mode, and complex 2 has stronger binding ability than complex 1. The in vitro cytotoxicity has been tested against the human lung adenocarcinoma cell line A-549, cisplatin-resistant cell line A-549/CDDP, and human breast adenocarcinoma cell line MCF-7. Complex 2 is more cytotoxic than complex 1, and both of them show higher cytotoxicity than the parent ligands alone. Compared with cisplatin, the two cobalt(II) complexes are more active against A-549/CDDP and MCF-7 cell lines at most experimental concentrations. Notably, although complex 2 is found to be less effective than cisplatin against the parent cell line A-549, it is much more effective than cisplatin against the resistant cell A-549/CDDP.     

Cytotoxic Polyhydroxylated Oleanane Triterpenoids from Cissampelos pareira var. hirsuta

Three new polyhydroxylated oleanane triterpenoids, cissatriterpenoid A−C (1−3), along with one known analogue (4), were isolated from the whole plant of Cissampelos pareira var. hirsuta. Their chemical structures were elucidated by extensive spectroscopic data (IR, HR-ESI-MS, ¹H-NMR, ¹³C-NMR, DEPT, ¹H-¹H COSY, HSQC, HMBC, NOESY) and the microhydrolysis method. The isolation of compounds 1–4 represents the first report of polyhydroxylated oleanane triterpenoids from the family Menispermaceae. All isolated compounds were evaluated for their cytotoxicity against five human cancer cell lines, and the inhibitory activity against NO release in LPS-induced RAW 264.7 cells. Compound 3 showed the most potent cytotoxic activities against the A549, SMMC-7721, MCF-7, and SW480 cell lines, with IC₅₀ values of 17.55, 34.74, 19.77, and 30.39 μM, respectively, whereas three remaining ones were found to be inactive. The preliminary structure–activity relationship analysis indicated that the γ-lactone ring at C-22 and C-29, and the olefinic bond at C-12 and C-13 were structurally required for the cytotoxicity of polyhydroxylated oleanane triterpenoids against these four cell lines. Based on lipid-water partition coefficients, compound 3 is less lipophilic than 1 and 4, which agrees with their cytotoxic activities. This confirms the potential of C. pareira var. hirsuta in the tumor treatment.     

Synthesis,cytotoxicity, apoptosis and molecular docking studies of novel phenylbutyrate derivatives as potential anticancer agents

Phenylbutyrate (PB), a small aromatic fatty acid, has been known as an interesting compound with the ability of anti-proliferation and cell growth inhibition in cancer cells. In the present study, a series of PB derivatives were synthesized by Passerini multicomponent reaction and their cytotoxic activities against various human cancer cell lines including A549 (non-small cell lung cancer), MDA-MB-231 (breast cancer), and SW1116 (colon cancer) were evaluated. The results revealed that B9, displayed significantly higher in vitro cytotoxicity with IC₅₀ of 6.65, 8.44 and 24.71 μM, against A549, MDA-MB-231 and, SW1116, respectively, in comparison to PB. The effects of these compounds on the proliferation of MCF-10A as non-tumoral breast cell line, showed good selectivity of the compounds between tumorigenic and non-tumorigenic cell lines. Moreover, B9 has indicated apoptosis-inducing activities to MDA-MB-231 cancer cell line in a dose-dependent manner. The molecular docking studies of the synthesized compounds on pyruvate dehydrogenase kinase 2 (PDK2; PDB ID: 2BU8) and histone deacetylase complex (HDAC; PDB ID: 1C3R), as the main targets of PB were applied to predict the binding sites and binding orientation of the compounds to these targets.     

Synthesis and cytotoxicity studies of quinoline-3-carbonitrile derivatives

<正>A series of quinoline-3-carbonitrile derivatives were designed and synthesized.Their cytotoxicity in vitro against four cancer cell lines(A549,HT-29,MDA-MB-231 and SMMC-7721) were evaluated by standard MTT assay.The pharmacological results showed that most of the prepared compounds displayed excellent selective cytotoxicity toward SMMC-7721 cell line.Among them, compounds 7c,7e,11b,11f and 11g were more active than Gefitinb against SMMC-7721 cell line.     

A new 12,17-cyclo-labdane diterpenoid from the twigs of Dacrycarpus imbricatus

A new 12,17-cyclo-labdane diterpenoid, podoimbricatin C (1), along with 15 known compounds was isolated from the twigs of Dacrycarpus imbricatus. Their structures were elucidated by means of extensive spectroscopic analysis. Compound 1 is the second example of the unusual 12,17-cyclo-labdane diterpenoids. It showed no inhibitory effects against five human tumour lines (HL-60, SMMC-7721, A-549, MCF-7 and SW-480).     

Sphingofungins G and H: new five-membered lactones from Aspergillus penicilliodes Speg.

Two new sphingofungins G (1) and H (2) with a five-membered lactone ring were identified from the solid-state fermentation of Aspergillus penicilliodes Speg., a dominant microorganism isolated previously from the post-fermentation of ripe Pu-er tea, together with six known metabolites. Their structures were elucidated by extensive spectroscopic methods. All of them were isolated from the mycelia culture of A. penicilliodes for the first time. The known compound, trypacidin, exhibited potent cytotoxities against five human cancer cell lines, e.g. myeloid leukemia HL-60, lung cancer A-549, hepatocellular carcinoma SMMC7721, breast cancer MCF-7, and colon cancer SW480, with IC₅₀ values of 0.55, 11.45, 10.95, 3.58, and 3.49 μM, resp., while cisplatin as the positive control, with IC₅₀ values of 8.63, 24.15, 21.99, 27.29, and 23.61 μM, resp.     

Furanocoumarins with potential antiproliferative activities from Clausena lenis

A phytochemical investigation on the stems and leaves of Clausena lenis led to the isolation of a new furanocoumarin, clauselenisin A (1), together with five known analogues (2–6). The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with data reported in the literature. All known compounds (2–6) were isolated from C. lenis for the first time. All isolated compounds were evaluated for their their antiproliferative activities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1–6 showed significant antiproliferative effects with IC₅₀ values ranging from 0.36 to 16.48 μM.     

New pyrazinoquinazoline alkaloids Isolated from a culture of Stenotrophomonas maltophilia QB-77

Two new pyrazinoquinazoline alkaloids, epi-fiscalin D (1) and epi-fiscalin E (2), as well as three known analogues, norquinadoline A (3), quinadoline A (4), and fiscalin C (5), were isolated from ethyl acetate extract of the fermentation broth of Stentrophomonas maltophilia QB-77. The structures of new compounds were elucidated on the basis of extensive spectroscopic data analysis including UV, HRESIMS, and 1D and 2D NMR experiments. All the isolated compounds were tested for their in vitro cytotoxicity against five human cancer cell lines (SMMC-7721, MCF-7, HL-60, SW480, and A-549) and antibacterial activities against Bacillus subtilis, Escherichia coli, and Staphylococcus aureus.     

Iodine-catalyzed three-component one-pot synthesis of novel 1,8-dioxo-decahydroacridines derivatives bearing benzene sulfonamide moiety

An efficient synthetic method for 1,8-dioxo-decahydroacridines derivatives bearing the biologically active sulfonamide moiety is described. Aromatic aldehyde reacted with 5,5-dimethyl-1,3-cyclohexanedione and sulfanilamide, with molecular iodine as catalyst, to give 1,8-dioxo-decahydroacridines derivatives in high to excellent yield. The structures of these compounds were established on the basis of elemental (C, H and N) and spectral analysis (¹H NMR, ¹³C NMR, MS and FTIR). All the compounds were tested for their cytotoxic activity in vitro against three human tumor cell lines: human mammary cancer cells (MCF-7), human cervical carcinoma cells (Hela), and human lung cancer cells (A549) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Most of them showed moderate to potent cytotoxic activity against the tested cell lines. Among them, the most active compound 4e exhibited more efficient activity (10.92 μM) against MCF-7 cells than cisplatin (11.06 μM).     

Nortriterpene constituents from Schisandra sphenanthera

Nine new highly oxygenated nortriterpenoids, pre-schisanartanins E–J (1–6) and sphenadilactones D–F (7–9), together with 17 known ones (10–26), have been isolated from the acetone extract of the roots and stems of Schisandra sphenanthera. The structures of the new metabolites were characterized on the basis of extensive spectroscopic analyses including 1D and 2D NMR experiments. These compounds were all evaluated for their cytotoxicity against HL-60, SMMC-7721, A549, MCF-7, and SW480 tumor cell lines.