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.     

Calaxanthones A-C,three new xanthones from the roots of Calophyllum calaba and the cytotoxicity

Three new xanthones, named calaxanthones A-C (1–3), along with 17 known xanthones (4–20) were isolated from the roots of Calophyllum calaba. Their structures were determined by spectroscopic analysis. All isolated compounds were evaluated for their cytotoxicity against five cancer cell lines (KB, HeLa S-3, HT-29, MCF-7 and HepG-2). Compound 3 showed potent cytotoxicity against all the five cancer cell lines with IC₅₀ values in the range of 0.82–5.04 μM. Furthermore, compound 6 showed potent cytotoxicity against KB, HeLa S-3 and HepG2 cells with IC₅₀ values of 7.06, 5.27 and 9.64 μM, respectively. Additionally, compound 7 showed potent cytotoxicity against KB cell with an IC₅₀ value of 4.62 μM.     

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.     

Two New Prenylated Xanthones from the Pericarp of Garcinia mangostana (Mangosteen)

Two new prenylated xanthones (=9H‐xanthen‐9‐ones), garcimangosxanthones D ( 1 ) and E ( 2 ), together with the six known xanthones 3 – 8 , were isolated from the pericarp of Garcinia mangostana. Their structures were determined by analysis of their spectroscopic data. All of the isolated compounds were biologically evaluated for their in vitro cytotoxic activity against A549, Hep‐G2, and MCF‐7 human‐cancer cell lines and antioxidant activity. Compound 1 exhibited moderate cytotoxicity against Hep‐G2 (IC₅₀=19.2 μM ) and weak cytotoxicity against MCF‐7 (IC₅₀=62.8 μM ) cell lines, and compound 2 showed moderate cytotoxicity against A549, Hep‐G2, and MCF‐7 cell lines with IC₅₀ values of 12.5–20.0 μM (Table 2). Both compounds 1 and 2 demonstrated a weak antioxidant activity with ferric reducing antioxidant power (FRAP) values of 41±7 and 130±4 μmol/g, respectively (Table 3).     

Triterpene tetraglycosides from the sea cucumber Stichopus horrens

Using various chromatographic separations, three triterpene tetraglycosides (1–3), including one new compound, namely stichorrenoside E (1) along with thelenotoside B (2) and deacetyl thelenotoside B (3), were isolated from the MeOH extract of the Vietnamese sea cucumber Stichopus horrens. Their structures were confirmed by spectroscopic experiments, such as 1D and 2D NMR and HR-ESI-MS. Deacetylated thelenotoside B (3) is firstly isolated as a natural product. Among these compounds, thelenotoside B (2) showed strong cytotoxicities against five human cancer cell lines as HepG2, KB, LNCaP, MCF7 and SK-Mel2 with the IC₅₀ values from 0.95 ± 0.08 to 1.90 ± 0.13 μM, whereas stichorrenoside E (1) and deacetyl thelenotoside B (3) exhibited significant activities with the IC₅₀ values from 6.87 ± 0.25 to 11.62 ± 1.05 μM.     

1,2-Benzisoxazole-3-acetamide derivatives as dual agents for DPP-IV inhibition and anticancer activity

Abstract

Herein, we have designed various benzisoxazole acetamide derivatives with and without glycine spacer as DPP-IV inhibitors. Compounds 9a–d and 11a–e were synthesized and screened for their in vitro DPP-IV inhibition. Compounds 11a and 11c showed moderate activity for DPP-IV inhibition, whereas other remained inactive at 25–200?µM concentrations. DPP-IV inhibition can be a good strategy for modulating diabetes and cancer; hence, we have screened compounds 9a–d and 11a–e for their anticancer activity using MTT assay against A549 and MCF7 cell lines. Compounds 9a–d without glycine spacer have shown good anticancer activity compared to compounds 11a–e with glycine spacer. Compound 9b has shown moderate activity with IC₅₀ values 4.72?±?0.72 and 4.39?±?0.809?µM against A549 and MCF7 cell lines, respectively. Interestingly, compound 9c with cyano group has shown very good anticancer activity with IC₅₀ 2.36?±?0.34?µM against MCF7 cell line as compared to fluorouracil with IC₅₀ 45.04?±?1.02?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.     

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.     

A new flavane acid from the fruits of Illicium verum

A new compound, illiciumflavane acid (1), along with 13 known compounds (2–14), were isolated from the fruits of Illicium verum Hook. F. Their structures were elucidated through various spectroscopic methods, including 1D NMR (¹H NMR, ¹³C NMR), 2D NMR (HMQC, HMBC and NOESY) and HRMS. The stereochemistry at the chiral centres was determined using CD spectrum as well as analyses of coupling constants and optical rotation data. Cytotoxicity evaluation of four compounds showed that illiciumflavane acid and (E)-1,2-bis(4-methoxyphenyl)ethene exhibited potential against A549 activities with IC₅₀ values of 4.63 μM and 9.17 μM, respectively.     

Anti-breast cancer triterpenoid saponins from the thorns of Gleditsia sinensis

One new triterpenoid saponin (1), as well as six known ones (2–7), were isolated from the ethanol extract of the thorns of Gleditsia sinensis. Their structures were elucidated by extensive spectroscopic analysis in conjunction with chemical evidence. Cytotoxic activity of compounds 1–6 was evaluated against human breast cancer MCF 7 cells in vitro by the MTT method. Our results revealed moderate activities for compounds 1–6 with IC₅₀ values of 18.43, 30.47, 18.46, 10.02, 30.76, and 17.32 μM, respectively. Furthermore, compounds 1, 3, 4, and 6 induced apoptosis in MCF 7 cell, with 1 and 6 causing late apoptosis of MCF 7 cells, while 3 and 4 acting oppositely.     

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.     

Synthesis and evaluation of antitumour activity in vitro and in vivo of chrysin salicylate derivatives

A series of chrysin salicylate derivatives as potential antitumour agents were synthesised and evaluated their antitumour activities in vitro and in vivo. Most of the compounds exhibited moderate to good activities against MCF-7 cells, HepG2 cells, MGC-803cells and MFC cells. Among them, compound 3f showed the most potent activity against MGC-803 cells and MFC cells with IC₅₀ values of 23.83 ± 3.68 and 27.34 ± 5.21 μM, respectively. The flow cytometry assay reconfirmed that compound 3f promoted the occurrence of tumour cells’ G1/S block under the inhibiting effect of compound 3f. Compound 3f possessed higher antitumour efficacy in tumour-bearing mice, compared with the positive control 5-Fu and the blank control saline.     

Cytotoxicity of syringin and 4-methoxycinnamyl alcohol isolated from Foeniculum vulgare on selected human cell lines

This study was carried out to determine the cytotoxic effect of seven plant extracts and the isolated compounds – syringin and 4-methoxycinnamyl alcohol – on cancerous and non-cancerous cells. The ethanol extract of Foeniculum vulgare was found to exhibit the most significant toxicity with an IC₅₀ value of 19.97 μg/mL on HeLa cells. Bioassay-guided fractionation led to the isolation of two compounds, syringin (1) and 4-methoxycinnamyl alcohol (2). Both compounds showed toxicity against MCF-7, HeLa and DU145 cancer cell line. The results showed that compound 2 showed high toxicity against all the cancer cell lines with IC₅₀ values of 14.24, 7.82 and 22.10 μg/mL, respectively. 4-Methoxycinnamyl alcohol also showed no apoptotic effect in cell cycle analysis after 48 h at a concentration of 10 μg/mL. However, DNA fragmentation study revealed that necrosis took place at a concentration of 10 μg/mL after 48 h exposure.     

Synthesis,cytotoxicity, and interaction with DNA of platinum(II) complexes of (1R,2R)-N1-2-amyl-1,2-diaminocyclohexane

(1R,2R)-N¹-2-amyl-1,2-diaminocyclohexane, which has an amyl substituent as compared with 1,2-diaminocyclohexane, was used as the carrier group to construct three platinum(II) complexes. MTT assay revealed that the complexes showed decent cytotoxicity against all of the four tested tumor cell lines with the IC₅₀ values ranging from 1.08 to 253.36 μM. Particularly, the IC₅₀ values of 2 against A549 and HCT-116 reached 3.32 and 1.08 μM, respectively, which were much lower than those of cisplatin and oxaliplatin. Flow cytometry demonstrated that 2 inhibited HepG2 cells proliferation and caused cytotoxicity by inducing apoptosis and arresting cells in the G2 phase. Furthermore, agarose gel electrophoresis showed that 2 had the ability to interact with DNA in a manner different from cisplatin and oxaliplatin, indicating the carrier ligand with an alkyl moiety had an influence on the action mode of the complex.     

Cytotoxicity of benzophenanthridine alkaloids from the roots of Zanthoxylum nitidum (Roxb.) DC. var. fastuosum How ex Huang

This work aimed to investigate benzophenanthridine from the roots of Zanthoxylum nitidum (Roxb.) DC. var. fastuosum How ex Huang for the first time. Thirteen benzophenanthridines were isolated, and our results of the cytotoxic activities indicated that compound 6 exhibited the best potency against A549, Hela, SMMC-7721 and EJ, with the IC₅₀ values of 27.50, 37.50, 16.95 and 60.42 μM, respectively. Compounds 7 and 11 also showed strong cytotoxicity when tested against the four human cancer cell lines (A549, Hela, SMMC-7721 and EJ), while only compounds 12 and 13 displayed cytotoxicity in inhibiting BALL-1 proliferation among all the compounds. These results suggested that benzophenanthridines may become a valid alternative of potential basis for new anti-proliferative agents.     

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.     

Antiproliferative,Cytotoxic, and Apoptotic Effects of New Benzimidazole Derivatives Bearing Hydrazone Moiety

In order to take the advantages of the anticancer properties of benzimidazoles and hydrazones, we synthesized new 4‐(5‐chloro‐1H‐benzimidazol‐2‐yl)‐benzoic acid benzylidene hydrazide derivatives ( 3a–3t ) and evaluated their anticancer activity against A549 (human lung adenocarcinoma) and MCF‐7 (human breast adenocarcinoma) cells. The structures of the compounds ( 3a–3t ) were confirmed by IR, ¹H‐NMR, ¹³C‐NMR, mass spectroscopy, and elemental analyses. Antiproliferative activities of the compounds were evaluated using MTT assay, BrdU method, and flow cytometric analysis. In addition, with purpose of determining selectivity the cytotoxic activities of the final compounds were screened against healthy NIH3T3 cell line (mouse vembryonic fibroblast cells). Among the tested compounds 3e and 3f showed significant cytotoxic activity against A549 and MCF‐7 cancer cells with an IC₅₀ value of 0.0316 μM. Furthermore, compound 3p showed remarkable cytotoxic activity against MCF‐7 comparing with standard drug cisplatin. Annexin V‐FITC assay also suggested that this compounds induced cell death by apoptosis.     

A new sterol from the Vietnamese marine sponge Xestospongia testudinaria and its biological activities

A new sterol, langcosterol A (1), together with two known sterols 2 and 3, were isolated from the marine sponge Xestospongia testudinaria collected in Vietnam. Their chemical structures were elucidated on the basis of extensive spectroscopic analyses and comparisons with published data. The new compound 1 and the known compound 3 exhibited moderate cytotoxic activities against three human cancer cell lines (A549, lung cancer; MCF7, breast cancer; HeLa, cervical cancer) and a human normal cell line (WI-38 fibroblast), with IC₅₀ values ranging from 29.0 to 68.0 μM.     

Antileishmanial diterpenoid alkaloids from Aconitum spicatum (Bruhl) Stapf

The crude extracts of tubers of Aconitum spicatum (Bruhl) Stapf were investigated for in vitro antileishmanial activity against Leishmania major. The dichloromethane extract at pH 2.5 showed antileishmanial activity with IC₅₀ value of 27.10 ± 0.0 μg/mL. Chromatographic purification of the dichloromethane extract led to isolation of three C-19 norditerpenoid alkaloids indaconitine (1), chasmaconitine (2) and ludaconitine (3). Compounds 3 and 2 showed antileishmanial activity with IC₅₀ = 36.10 ± 3.4 and 56.30 ± 2.1 μg/mL, respectively. Compound 1 was less effective (IC₅₀ > 100 μg/mL). The cytotoxicity of compounds 1, 2 and 3 studied against MCF7, HeLa and PC3 cancer cell lines and 3T3 normal fibroblast cell line did not show cytotoxicity at 30 μM.     

A new rearranged abietane diterpene from Clerodendrum inerme with antioxidant and cytotoxic activities

Eight compounds were isolated from the leaves of Clerodendrum inerme, including one new rearranged abietane diterpene, crolerodendrum B (1). Their structures were determined by means of spectroscopic methods including one-dimensional and two-dimensional nuclear magnetic resonance (1-D and 2-DNMR), high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS) and circular dichroism (CD). The DPPH radical scavenging and cytotoxic activities of isolated compounds against MCF7 (breast), HCT116 (colon) and B16F10 (melanoma) cancer cell lines were evaluated. Compounds 1, 3 and 4 exhibited strong DPPH radical-scavenging effects (ED₅₀ values of 17.6 ± 2.1, 10.1 ± 0.8 and 11.3 ± 0.3 μM, respectively) and 4 showed strong cytotoxicity against the HCT116 cell line (IC₅₀ = 3.46 ± 0.01 μM).