Synthesis and in vitro cytotoxicity of platinum(II) complexes with chiral N-monosubstituted 1,2-cyclohexyldiamine derivatives as the carrier groups

Eight platinum(II) complexes with the new chiral ligands, (1R,2R)-N ¹-(pyridine-2-ylmethyl) cyclohexane-1,2-diamine (R) or (1S,2S)-N ¹-(pyridine-2-ylmethyl) cyclohexane-1,2-diamine (S) as the carrier groups were designed, synthesized, and spectrally characterized. All platinum(II) complexes showed much better aqueous solubility than cisplatin and oxaliplatin. In vitro cytotoxicity of the compounds against human HepG-2, MCF-7, A549, and HCT-116 cell lines was evaluated. Results indicate that all compounds with R as the carrier group showed cytotoxicity against HCT-116, A549, and MCF-7 cell lines; however, all compounds with S as carrier group exhibited disappointing cytotoxicity against tested cell lines. Compound R2, bearing ClCH₂COO^- as leaving group, exhibited better cytotoxicity than that of carboplatin against A549 and MCF-7 cell lines and also showed close activity to oxaliplatin against HCT-116 cell line.     

Synthesis and in vitro cytotoxicity of novel dinuclear platinum(II) complexes containing a chiral tetradentate ligand

A series of novel dinuclear platinum(II) complexes with a chiral tetradentate ligand, (1R,1′R,2R,2′R)-N¹,N¹′-(1,2-phenylenebis(methylene))dicyclohexane-1,2-diamine (HL), and mono-carboxylic acid derivatives as ligands have been designed, synthesized, and characterized. In vitro cytotoxicity evaluation of synthesized complexes against human HepG-2, A549, HCT-116, and MCF-7 cancer cell lines has been conducted by MTT assays. All compounds showed antitumor activity to HepG-2 and HCT-116 cell lines. Compound L2 exhibited better cytotoxicity than that of carboplatin against HepG-2 and A549 cell lines and also showed comparable activity against HCT-116 cell line.     

(1iR, 1iiR, 2iR, 2iiR)-Ni, Nii-(1,3-亚苯基双(亚甲基))环己烷-1,2-二胺作为配体的双核铂配合物的合成及其抗癌活性

以(1ⁱR,1ⁱⁱR,2ⁱR,2ⁱⁱR)-Nⁱ, Nⁱⁱ-(1,3-亚苯基双(亚甲基))环己烷-1,2-二胺(HL)作为配体,设计并合成了7种双核铂配合物,并利用IR,¹H NMR,¹³C NMR,ESI-MS和元素分析等进行了表征。通过MTT法测定目标双核铂配合物对人类HepG-2,A549,HCT-116和MCF-7四种癌细胞系的细胞毒性。结果表明,所有的化合物对HepG-2,A549和HCT-116细胞系均表现了良好的细胞毒活性,但对MCF-7细胞系均无活性。其中,以3-羟基环丁烷-1,1-二羧酸为离去基团的配合物P7对HepG-2和A549细胞系的活性优于卡铂,对HCT-116细胞系的活性接近于奥沙利铂。     

(1iR,1iiR,2iR,2iiR)-Ni,Nii-(1,3-亚苯基双(亚甲基))环己烷-1,2-二胺作为配体的双核铂配合物的合成及其抗癌活性

以(1ⁱR,1ⁱⁱR,2ⁱR,2ⁱⁱR)-Nⁱ,Nⁱⁱ-(1,3-亚苯基双(亚甲基))环己烷-1,2-二胺(HL)作为配体,设计并合成了7种双核铂配合物,并利用IR,¹H NMR,¹³C NMR,ESI-MS和元素分析等进行了表征。通过MTT法测定目标双核铂配合物对人类HepG-2,A549,HCT-116和MCF-7四种癌细胞系的细胞毒性。结果表明,所有的化合物对HepG-2,A549和HCT-116细胞系均表现了良好的细胞毒活性,但对MCF-7细胞系均无活性。其中,以3-羟基环丁烷-1,1-二羧酸为离去基团的配合物P7对HepG-2和A549细胞系的活性优于卡铂,对HCT-116细胞系的活性接近于奥沙利铂。     

Preparation and in vitro cytotoxicity of oxaliplatin derivatives with chiral amino acid as the carrier group

Eight oxaliplatin derivatives with chiral amino acid, 2-{[(1R,2R)-2-aminocyclohexyl]amino}propanoic acid, as the carrier group, were designed, synthesized, and spectrally characterized by IR, ¹H NMR, MS spectra, and microanalyses. In vitro cytotoxicities against human HepG-2, MCF-7, A549, and HCT-116 cell lines were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazo-liumbromide assay. Results indicated that all compounds exhibited sensitivity to HepG-2 cell line, and among them, compounds P3 and P4 which have CH₃(CH₂)₆COO^– and CH₃(CH₂)₈COO^– as the leaving groups, respectively, gave better antitumor activity than carboplatin against HepG-2 and A549 cell lines.     

Studies on the constituents of Cimicifuga foetida collected in Guizhou Province and their cytotoxic activities

Two new triterpenoids and a chromone glycoside, namely, 24-epi-cimigenol-3-one (1), foetinoside (2), cimifugin-4'-O-[6″-feruloyl]-β-D-glucopyranoside (3), together with 18 known compounds, were isolated from the rhizomes of Cimicifuga foetida L. collected in Guizhou Province, China. All of the compounds were identified by spectroscopic methods, as well as chemical methods. In the in vitro cytotoxicity evaluation of these compounds against 5 human cancer cell lines, cimigenol (8) exerted the most potent cytotoxic activity against SMMC-7721 (7.87?μM) and A-549 (12.16 μM), while cimiacerin B (9) also showed obvious cytotoxicity against the A-549 cell line, with an IC(50) value of 16.77?μM.     

Triterpene Saponins from <i>Pleurospermum kamtschaticum</i> and Their Biological Activity

Eleven new triterpene saponins (1-11), together with fourteen known triterpene and triterpene saponins (12-25) were isolated from a MeOH extract of Pleurospermum kamtschaticum HOFFMANN (Umbelliferae). The chemical structures of the new compounds (1-11) were determined by means of MS, ¹H-NMR, ¹³C-NMR, correlated spectroscopy (COSY), heteronuclear multiple bond correlation (HMBC), total correlated spectroscopy (TOCSY) and nuclear Overhauser effect spectroscopy (NOESY) to be pleurosaponin A (1)-K (11). The isolated compounds were tested for their cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, HCT15) in vitro using the sulforhodamine B bioassay (SRB) assay. All compounds showed little cytotoxicity against tested cell lines (IC50 >30?μM).     

Design, Synthesis and Anticancer Activities of Diaryl Urea Derivatives Bearing <i>N</i>-Acylhydrazone Moiety

A new series of diaryl urea derivatives bearing N-acylhydrazone moiety were designed and synthesized. All the target compounds were evaluated for their cytotoxic activities in vitro against human lung adenocarcinoma epithelial cell line (A549), human breast cancer cell line (MDA-MB-231) and human leukemia cell line (HL-60) by standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Several compounds (1a, 1f and 1h) were further evaluated against human embryonic fibroblast, lung-derived cell line (WI38). The pharmacological results indicated that some compounds exhibited promising anticancer activities. In particular, compound 1f showed the most potent cytotoxicity against the tested three cell lines with IC50 values of 0.41?μM, 0.24?μM and 0.23?μM, respectively.     

Cytotoxicity of constituents from Mexican propolis against a panel of six different cancer cell lines

The cytotoxicity of 39 compounds, including eighteen flavonoids (flavanones, 1-10; flavones, 11-17; flavanol, 18), sixteen phenolic acid derivatives (aromatic acids, 19-24; aldehyde, 25; esters, 26-34) and five glycerides (35-39), isolated from Mexican propolis, were evaluated against a panel of six different cancer cell lines; murine colon 26-L5 carcinoma, murine B16-BL6 melanoma, murine Lewis lung carcinoma, human lung A549 adenocarcinoma, human cervix HeLa adenocarcinoma and human HT-1080 fibrosarcoma. A phenylpropanoid-substituted flavanol, (2R,3S)-8-[4-phenylprop-2-en-1-one]-4',7-dihydroxy-3',5-dimethoxyflavan-3-ol (18), showed the most potent cytotoxicity against A549 cells (IC50, 6.2 microM) and HT-1080 cells (IC50, 3.9 microM), stronger than those of the clinically used anticancer drug, 5-fluorouracil (IC50, 7.5 microM and 5.4 microM, respectively). Based on the observed results, the structure-activity relationships are discussed.     

Three new megastigmane glucopyranosides from the Cardamine komarovii

Three new megastigmane glucopyranosides, komaroveside A [(3S,4R,5Z,7E)-3,4-dihydroxy-5,7-megastigmadien-9-one-3-O-β-D-glucopyranoside] (1), komaroveside B [(3S,4S,5S,6R,7E)-5,6-epoxy-3,4-dihydroxy-7-megastigmen-9-one-3-O-β-D-glucopyranoside] (2) and komaroveside C [(3S,4S,5S,6R,7E,9S)-5,6-epoxy-3,4,9-trihydroxy-7-megastigmen-3-O-β-D-glucopyranoside] (3) were isolated, together with eight known compounds, from Cardamine komarovii. The identification of these compounds and the elucidation of their structures were based on 1D- and 2D-NMR spectral data analysis. The isolated compounds were tested for their cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, HCT15) in vitro using the sulforhodamine B bioassay.     

Design,synthesis and in vitro cytotoxicity of novel dinuclear platinum(II) complexes with a tetradentate carrier ligand

Four novel dinuclear platinum complexes with a tetradentate ligand, (1R,1′R,2R,2′R)‐N¹,N^1′‐(1,2‐phenylenebis(methylene))dicyclohexane‐1,2‐diamine, as the carrier group, have been designed, synthesized and characterized, and their in vitro cytotoxicity against HepG‐2, A549, HCT‐116 and MCF‐7 cell lines evaluated using MTT assay. Results indicate that the targeted dinuclear platinum complexes H1 , H2 , H3 , H4 exhibit significant growth inhibitory properties against HepG‐2, A549 and HCT‐116 cell lines, but none of them show activity against MCF‐7 cell line. Compound H4 shows better antitumor activity than carboplatin against HepG‐2, A549 and HCT‐116 cell lines. Copyright © 2015 John Wiley & Sons, Ltd.     

Cytotoxic activity of antioxidant constituents from Hypericum triquetrifolium Turra

The Sulforodamine B (SRB) assay was used to test cytotoxicity against four human cancer cell lines and one normal cell line of antioxidant constituents isolated from Hypericum triquetrifolium Turra. Methanolic extract and pure compounds were tested against the large cell lung carcinoma cell line COR-L23, the hepatocellular carcinoma cell line HepG-2, renal cell adenocarcinoma ACHN, the amelanotic melanoma cell line C32 and normal human foetal lung MRC5. The results showed that I3-II8-biapigenin exhibited strong cytotoxic activity (IC50 = 5.73 micro g mL(-1)) showing a certain degree of selectivity against the different cell types.     

Synthesis and antitumor activity of some new pyrazolo[1,5-a] pyrimidines

New series of pyrazolo[1,5-a]pyrimidine derivatives 7a-i, 11a-c and Schiff bases 13a-c were synthesized and screened for their in vitro antitumor activity against three human carcinoma cell lines, namely colorectal carcinoma (HCT116), prostate adenocarcinoma (PC-3) and liver carcinoma (HepG-2) using MTT cytotoxicity assay at 100 μg/mL. Some of the tested compounds displayed good anticancer activities against HCT-116 and PC-3 cells. Whereas, compounds 7d and 11a showed better antitumor activity than the rest of the compounds against both cell lines. A structure-activity relationship (SAR) has been discussed and structures of the newly synthesized compounds were confirmed by different spectral data (MS, IR, ¹H NMR and ¹³C NMR) and elemental analysis.     

Synthesis and antitumor activity of 1-acetyl-3-(4-phenyl)-4,5-dihydro-2-pyrazoline-5-phenylursolate and 4-chalcone ursolate derivatives

New 4-chalcone ursolate and 1-acetyl-3-(4-phenyl)-4,5-dihydro-2-pyrazoline-5-phenyl ursolate derivatives were synthesized by esterification of UA and chalcone or pyrazoline. The compounds were structurally confirmed by IR, ¹H NMR, ¹³C NMR, and HR-MS spectroscopy. The cytotoxicity of ten derivatives was evaluated against A549, SKOV3, and HepG2 cell lines by MTT assay. The result showed that several compounds were more potent than UA against A549 and SKOV3 cells; however, none of them were more potent than UA against HepG2.     

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.     

Novel antitumor dinuclear platinum (II) complexes with a new chiral tetradentate ligand as the carrier group

Seven dinuclear platinum(II) complexes with a novel chiral tetradentate ligand, (1R,1′R,2R,2′R)‐N¹,N^1′‐(1,4‐phenylenebis(methylene))dicyclohexane‐1,2‐diamine, were designed, synthesized and spectrally characterized. All the complexes were evaluated for their in vitro cytotoxicity against human HepG‐2, A549, HCT‐116 and MCF‐7 cancer cell lines. The results indicated that all compounds showed positive biological activity against HepG‐2, A549 and HCT‐116 cancer cell lines. In particular, compounds D7 and D2 showed better activity than carboplatin against HepG‐2 and A549 and compound D7 also showed an activity close to that of oxaliplatin. Copyright © 2015 John Wiley & Sons, Ltd.     

A new abietane diterpenoid glycoside from ajuga ovalifolia var. calantha

A new abietane diterpenoid glycoside, ajugaside B (1), along with three known compounds (2–4), were isolated from the whole plants of Ajuga ovalifolia var. calantha. The structure of the new compound (1) was elucidated by means of spectroscopic analyses (HRESIMS, IR, NMR and ECD). All of the isolated compounds were evaluated for their antitumor activities against MGC803, MCF-7, A549, HT29 and HepG2 cell lines. Compounds 3–4 showed moderate cytotoxicity against all tested cell lines with IC₅₀ values of 1.8–7.3?μM.     

Cytotoxic and anti-oxidant activities of lanostane-type triterpenes isolated from Poria cocos

A new lanostane-type triterpene, 29-hydroxypolyporenic acid C (8), was isolated from the dried sclerotia of Poria cocos together with eight other known compounds pachymic acid (1), dehydropachymic acid (2), 3-acetyloxy-16alpha-hydroxytrametenolic acid (3), polyporenic acid C (4), 3-epi-dehydropachymic acid (5), 3-epi-dehydrotumulosic acid (6), tumulosic acid (7), and dehydrotumulosic acid (9). The compounds were identified by spectral analysis and comparison with spectroscopic data reported in the literatures. Although none of the nine (1 to 9) compounds showed promising antioxidant activity, 1 through 6 and 8 showed good cytotoxicity against human lung cancer cell line A549 and human prostate cancer cell line DU145. Interestingly, all these compounds exhibited better cytotoxicity towards A549 than DU145 cells.     

New cytotoxic apigenin derivatives from Selaginella doederleinii

75%aqueous ethanol extract from the whole herbs of Selaginella doederleinii was isolated,and two new apigenin derivatives,doederflavones A(1) and B(2),together with ten known compounds(3-12) were characterized.Their structures were assigned by extensive spectroscopic methods including 1D/2D NMR and HR-ESIMS.Compounds 1-6 bear an aryl substituent at the C-8 or C-6 positions in ring A of apigenin skeleton.Compounds 1 and 2 were evaluated for their in vitro cytotoxicity against four human cancer cell lines A549,MCF-7,SMMC-7721,and LoVo,both of which exhibited significant cytotoxicity against A549 with IC_(50) values of 0.82 μmol/L and 1.32 μmol/L,respectively.     

Triterpenoids and diterpenoids from Viburnum chingii

Two new oleanane triterpenoids (1-2) and one new vibsane-type diterpenoid (3), together with 7 known compounds (4-10), were isolated from the leaves of Viburnum chingii. The structures of compounds 1-3 were elucidated by means of spectroscopic methods including extensive 1D- and 2D-NMR technique. Cytotoxicity of compounds 1-10 were tested against HL-60, SMMC-7721, A-549, SK-BR-3, and PANC-1 cell lines. Compound 3 showed significant cytotoxicity against HL-60, SK-BR-3, and PANC-1 cell lines.