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.     

Design and synthesis of novel 7-[(N-substituted-thioureidopiperazinyl)-methyl]-camptothecin derivatives as potential cytotoxic agents

Abstract

As part of continuing our research on diverse C-7 derivatives of camptothecin (CPT), 16 CPT derivatives bearing piperazinyl-thiourea chemical scaffold and different substituent groups have been designed, synthesized and evaluated in vitro for cytotoxicity against five tumor cell lines (A-549, MDA-MB-231, MCF-7, KB and KBvin). As a result, all the synthesized compounds showed promising in vitro cytotoxic activity against the five tumor cell lines tested, and were more potent than irinotecan. Importantly, compounds 13?g (IC₅₀ = 0.514?μM) and 13o (IC₅₀ = 0.275?μM) possessed similar or better antiproliferative activity against the multidrug-resistant (MDR) KBvin subline than that of topotecan (IC₅₀ = 0.511?μM) and merit further development as anticancer candidates for clinical trail. With these results in hand, we have a reason to conclude that incorporating piperazinyl-thiourea motifs into position-7 of camptothecin confers well cytotoxic activity against cancer cell lines, probably resulting in new anticancer drugs.     

Synthesis and in vitro antitumor activity of 1,3,4-oxadiazole derivatives based on benzisoselenazolone

A series of novel 1,3,4-oxadiazole derivatives based on benzisoselenazolone has been prepared and tested for antiproliferative activity in vitro against the cells of human cancer cell lines: SSMC-7721 (human liver cancer cell), MCF-7 (human breast cancer cell) and A549 (human lung cancer cell). All the compounds obtained exhibited antiproliferative activity and showed selective cytotoxicity against different cancer cells. Compounds 7d and 7i showed significant antiproliferative activities against MCF-7 cells, with IC50 values of 1.07 and 1.76?μM respectively. Compound 7d were found to be the most potent compound against SSMC-7721 cells, with IC50 values 4.46?μM.     

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.     

Two new benzophenones from endohydric moss Polytrichum Commune

Two new benzophenones (1 and 2), were isolated from the endohydric moss Polytrichum commune. Their structures were elucidated by spectroscopic methods including extensive 2?D NMR techniques. Compound 2 is the first example of benzophenone with a rare cyclopropylacetamide from the natural resources. Compounds 1 and 2 were screened their cytotoxicity against five cancer cell lines (HCT-116, A-549, MCF-7, HepG2, A-375,), and no cytotoxic activities were observed (IC₅₀ > 100?μM).     

Eudesmane and aromadendrane sesquiterpenoids from the Vietnamese soft coral Sinularia erecta

Using various chromatographic separations, eight sesquiterpenoids (1–8), including one new compound 3β,5α-dihydroxyeudesma-4(15),11-diene (1), were isolated from the MeOH extract of the Vietnamese soft coral Sinularia erecta. The structure elucidation was confirmed by spectroscopic experiments including 1D and 2D NMR and HR-ESI-MS. The cytotoxic activities against three human cancer cell lines (A-549, HeLa and PANC-1) of all isolated compounds were evaluated by MTT-based colorimetric assays. Compound 1 exhibited selective cytotoxicity against the A549 cell line with IC₅₀ of 14.79 ± 0.91 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).     

Cytotoxic triterpene saponins from the mangrove Aegiceras corniculatum

Using various chromatographic separations, sixteen compounds, including one new triterpene saponin named aegicoroside A (1), were isolated from the leaves of the Vietnamese mangrove Aegiceras corniculatum. Their structures were determined by spectroscopic methods such as 1D and 2D NMR and HR-ESI-MS. The cytotoxic activities of the isolated compounds against MCF7 (breast), HCT116 (colon), B16F10 (melanoma), and A549 (adenocarcinoma) cancer cell lines were also evaluated. Strong cytotoxicity was observed for sakurasosaponin (2) against all four cancer cell lines and for sakurasosaponin methyl ester (3) against MCF7, A549, and HCT116 cell lines with IC₅₀ values ranging from 2.89 ± 0.02 to 9.86 ± 0.21 μM.     

Design, Synthesis and Anticancer Activity of 4-Morpholinothieno[3,2-<i>d</i>]pyrimidine Derivatives Bearing Arylmethylene Hydrazine Moiety

Three series of 4-morpholinothieno[3,2-d]pyrimidine derivatives containing arylmethylene hydrazine moiety (11a-f, 13a-k and 15a-h) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. The synthesized compounds were evaluated for their cytotoxicity against three cancer cell lines (H460, HT-29, MDA-MB-231). Most of them exhibited moderate to significant cytotoxicity and high-selectivity against one or more cell lines, especially compounds 11c, 13b, 15f and 15g possessing dramatically increased cytotoxicity as compared with the positive controls, which were further evaluated for six other cancer cell lines and one normal cell line. The most promising compound 11c, bearing 3,4-methylenedioxy phenyl group, showed remarkable cytotoxicity against H460, HT-29 and MDA-MB-231 cell lines with IC50 values of 0.003?μM, 0.42?μM and 0.74?μM, which was 1.6- to 290-fold more potent than GDC-0941.     

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.

     

Synthesis, characterization and biological evaluation of platinum(II) complexes with a chiral N-monosubstituted 1,2-cyclohexyldiamine derivative

Eight platinum(II) compounds with a new chiral ligand, 2-(((1R,2R)-2-aminocyclohexylamino)methyl)phenol (HL), were designed, prepared and spectrally characterized. All compounds showed better aqueous solubility than cisplatin and oxaliplatin. In vitro cytotoxicity of these compounds against human HepG-2, MCF-7, A549 and HCT-116 cell lines was evaluated. Results indicated that all compounds showed cytotoxicity against A549 and HepG-2 cell lines. Particularly, compounds B1 and B8, which have CF?SO?? and (CH?)?COCH?COO(-) as leaving groups, respectively, exhibited better cytotoxicitiy than that of carboplatin in these two cell lines.     

Synthesis,characterization and biological evaluation of some novel sulfonylthiosemicarbazides

Abstract

A series of thiosemicarbazides were synthesized and structurally characterized by spectroscopic techniques (NMR, FT-IR) besides elemental analysis. These compounds were evaluated for their cytotoxicity against human breast cancer cell line MCF7 and prostate cancer cell line PC3 and nonmalignant fibroblast L929 cell line by MTT assay. Among the compounds, N-[2-(4-chlorophenyl)ethyl]-2-[(4-methylphenyl)sulfonyl]hydrazinecarbothioamide (3d) and 2-[(4-methylphenyl)sulfonyl]-N-[4-(trifluoromethoxy)phenyl]hydrazinecarbothioamide (3f) were found to display significant cytotoxicity with IC₅₀ of 13.87?μM (against PC3 cell line) and 1.47?μM (against MCF7 cell line), respectively. These compounds were non-cytotoxic to normal cell line with IC₅₀>100?μM. Western blotting studies demonstrated that compound 3f induced apoptosis and caused cell death in the MCF7 and PC3 cell lines via an increase in Bax protein expression and a slight decrease in Bcl-2 protein expression. The gene expression ratio Bax/Bcl-2 showed the induction of mitochondrial apoptosis in cancer cell lines. All of synthesized compounds have also been tested for antioxidant activity and all compounds achieved strong inhibition of the DPPH radical. These findings showed that compound 3f, displays potential to be further explored in the development of new anticancer agents.     

1H and 13C NMR assignments of two new indolic enamide diastereomers from a mangrove endophytic fungus Aspergillus sp

Terpeptin A (1) and B (2), two new members of the indolic enamides, along with three known compounds (3-5) were identified from a strain of Aspergillus sp. (w-6), an endophytic fungus associated with Acanthus ilicifolius. The complete (1)H and (13)C NMR assignments for these compounds were carried out using (1)H, (13)C, DEPT, COSY, HMQC, and HMBC NMR experiments. Terpeptin A and B exhibited modest cytotoxicity against A-549 cell line.     

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.     

Two new 5,6-epoxysterols from calcareous marine sponge Leucetta chagosensis

Chemical investigation on CH₂Cl₂ extract of the marine sponge Leucetta chagosensis, collected from the South China Sea, afforded two new 5,6-epoxysterols, 5α,6α-epoxycholesta-8(14),22(E)-diene-3β,7α-diol (1) and (24R)-24-ethyl-5α,6α-epoxycholesta-8(14),22(E)-diene-3β,7α-diol (2) along with ten known related steroid analogs (3–12). Their structures were elucidated on the basis of NMR spectroscopic analyses, and comparison with the literature. All isolates were tested for cytotoxicity against three tumor cell lines only known compounds 11 and 12 exhibited notable cytotoxic activity against A549 (IC₅₀: 3.0 and 5.6?μM), PC9 (2.0 and 15.6?μM), and MCF-7 (9.4 and 11.8?μM) cell lines, respectively.     

Three new diterpenes from Jatropha curcas

Jatrophalactone (1) and jatrophalone (2), together with jatrophadiketone (3), a 6/6/6 tricyclic diterpene transformed from rhamnofolane skeleton, have been isolated from the methanolic extract of Jatropha curcas. The structures were established on the basis of extensive spectroscopic methods and further confirmed by X-ray crystallographic analysis. The cytotoxicity against selected cell lines was evaluated. Among them, compound 1 displayed cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cell lines with IC₅₀ values of 8.5, 20.6, 19.7, 20.1, and 19.2 μM, respectively. The possible biosynthetic pathways for 1 and 3 are proposed.     

Synthesis and in vitro cytotoxic evaluation of 2-hydrazinylpyrido[2,3-b]pyrazin-3(4H)-one derivatives

A series of novel 2-hydrazinylpyrido[2,3-b]pyrazin-3（4H）-one derivatives were synthesized and evaluated for their cytotoxic activities against A549,MDA-MB-231 and HT-29 cell lines in vitro.Pharmacological data indicated that compounds 5b,5c,10a and 10g possessed marked cytotoxicity,especially 10a(with IC₅₀ values of 0.81,2.56 and 1.63μmol/L against A549,MDA-MB- 23 1 and HT29 cell lines,respectively),which had emerged as a lead compound.     

Cytotoxic compounds from the leaves of Gaillardia aristata Pursh. growing in Egypt

Ten compounds, neopulchellin (1), 6α- hydroxyneopulchellin (2), β-sitosterol-3-O-β-D-glucoside (3), apigenin (4), quercitin (5), eupafolin (6), kaempferol-3-methoxy-7-O-α-L-rhamnoside (7), apigenin-7-O-β-D-glucopyranoside (8), α-amyrin (9) and β-sitosterol (10), were isolated from the leaves of Gaillardia aristata by applying bioassay guided fractionation. The cytotoxicity was traced against two human cancer cell lines (breast (MCF7) and colon (HCT116)). The highest cytotoxicity was revealed by compounds 1 and 2 (isolated from chloroform extract); with IC(50) values of 0.43, 0.32?μg?mL(-1) against MCF7 and 0.46, 0.34?μg?mL(-1) against HCT116, respectively. Compounds 9 and 10 (isolated from the n-hexane extract) exhibited lower IC(50) values of 3.05, 2.35?μg?mL(-1) against MCF7 and 3.05, 2.35?μg?mL(-1) against HCT116, respectively, while compounds 4-7 obtained from the ethyl acetate extract revealed the lowest cytotoxicity. Identification of the aforementioned compounds was carried out on the basis of their physico-chemical properties and spectral analysis (UV, EI/MS, 1D and 2D).     

Four New 1,4‐Benzoquinone Derivatives and One New Coumarin Isolated from Ardisia gigantifolia

Four new 1,4‐benzoquinone derivatives, belamcandaquinones J ( 1 ), K ( 2 ), L ( 3 ), and M ( 4 ), and one new coumarin, 5 , were isolated from the rhizome of Ardisia gigantifolia. Their structures were established by means of spectroscopic methods, and their cytotoxicity was tested in vitro against the cell lines PC‐3, EMT6, A549, Hela, RM‐1, and SGC7901. In comparison with cisplatin, compound 5 showed strong cytotoxicity with an IC₅₀ value of <30 μM against the cell lines PC‐3 and A549. Compounds 1 – 4 showed no cytotoxicity against all cell lines.     

Chemical constituents,cytotoxic and antioxidant activities of extract from the rhizomes of Osmunda japonica Thunb

Abstract

Thirty-three compounds (1–33) were isolated from the rhizomes of Osmunda japonica. Their structures were elucidated on the basis of spectral analysis and identified as ent-kaurene terpenoids (1–3), anthraquinones (4–8), flavonoids (9–12), steroids (13–15), and other compounds (16–33). Compound 1–14, 19–27 were isolated from the genus osmunda for the first time. Compound 28–29 were isolated from the plant for the first time. Cytotoxicities of all compounds against Hela, HepG2 and A549 cell lines were measured by MTT assay, and their antioxidant activities were determined by DPPH and ABTS radical scavenging assays. Compound 2 exhibited potent cytotoxicity against Hela, HepG2 cell lines with IC₅₀ values of 9.31 and 9.66?μM, respectively. Compound 9 showed good antioxidant activity. The Trolox-equivalent antioxidant capacity (TEAC) value was 0.95?mM in ABTS assay, and the IC₅₀ value was 18.63?μM in DPPH assay.