Steroidal saponins with cytotoxic activity from the rhizomes of Paris polyphylla var. yunnanensis

Two previously unreported spirostanol saponins, dianchonglouosides A and B (1 and 2), along with 7 known steroidal saponins (3–9) were isolated from the rhizomes of Paris polyphylla var. yunnanensis. Their structures were elucidated by extensive spectroscopic analysis (MS, 1D, and 2D NMR), and chemical methods. The cytotoxic activities of the isolated compounds 1–9 were also evaluated against two human cancer cell lines (HEK293 and HepG2). The results showed that compound 7 had the strongest cytotoxic activity against the two cancer cell lines with the IC₅₀ values of 0.6 and 0.9 μM, respectively.     

Cytotoxic cycloartane triterpenoids from the leaves of Markhamia stipulata var. canaense

From the most cytotoxic fraction of the ethyl acetate extract of Markhamia stipulata var. canaense V.S. Dang leaves, two new cycloartane-type triterpenoids, named Markhacanasin A (1) and Markhacanasin B (2); were isolated by various chromatographic methods Their structures were elucidated by IR, UV, HR-ESI–MS, NMR (1D & 2D) experiments. The cytotoxicity of two new compounds against five human cancer cell lines (HeLa, HepG2, MCF-7, Jurkat and NCI-H460) were evaluated by SRB assay. As results, 1 exhibited significant cytotoxic activity against all cancer cell lines (IC₅₀ ranged from 14.72 to 29.55 μM) while 2 did not show activity.     

Synthesis,cytotoxic activity,and tubulin polymerization inhibitory activity of new pyrrol-2(3H)-ones and pyridazin-3(2H)-ones

A series of new pyrrol-2(3H)-ones 4a-f and pyridazin-3(2H)-ones 7a-f were synthesized and characterized using different spectroscopic tools. Some of the tested compounds revealed moderate activity against 60 cell lines. The E form of the pyrrolones 4 showed good cytotoxic activity than both the Z form and the corresponding open amide form. Furthermore, the in vitro cytotoxic activity against HepG2 and MCF-7 cell lines revealed that compounds (E)4b, 6f and 7f showed good cytotoxic activity against HepG2 with IC₅₀ values of 11.47, 7.11 and 14.80 μM, respectively. Compounds (E)4b, 6f, 7d and 7f showed a pronounced inhibitory effect against cellular localization of tubulin. Flow cytometric analysis indicated that HepG2 cells treated with (E)4b showed a predominated growth arrest at the S-phase compared to that of G2/M-phase. Molecular modeling study using MOE® program indicated that most of the target compounds showed good binding of β-subunit of tubulin with the binding free energy (dG) values about −10 kcal/mole.     

New phenylpropanoids with cytotoxic activities from Drypetes hainanensis

Phytochemical investigation on Drypetes hainanensis has resulted in the isolation of three new phenylpropanoids, named drypetesins A–C (1–3). Their structures were elucidated by applying various spectroscopic techniques (NMR, UV, IR, MS, and CD). The antiproliferative activities of these compounds were evaluated in vitro against three cultured cancer cell lines. Those new isolates exhibited potent cytotoxic activities against human hepatoma (HepG2), human breast adenocarcinoma (MCF-7), and human lung carcinoma (A-549) cancer cell lines with IC₅₀ value range 5.6–14.8 μM.     

Phenylpropanoids from Juglans mandshurica exhibit cytotoxicities on liver cancer cell lines through apoptosis induction

Three new phenylpropanoids (1–3) together with six known congeners (4–9) were isolated from the bark of Juglans mandshurica Maxim using anti-hepatoma activity as a guide. Their structures were determined by comprehensive NMR and HRESIMS spectroscopic data analyses. All the isolated compounds were evaluated for their growth inhibitory activities against two kinds of liver cancer cell lines (HepG2 and Hep3B). Among them, compound 4 showed moderate cytotoxic activities against HepG2 and Hep3B cell lines with IC₅₀ values of 58.58 and 69.87 μM. Compound 5 exhibited 50% cell death rate in HepG2 and Hep3B cell lines at 63.70 and 46.45 μM, respectively. Further observation of morphological changes and Western blot demonstrated that compounds 4 and 5 exhibited their cytotoxic activities through the induction of apoptosis. A structure-activity relationship study suggested that an α, β-unsaturated aldehyde might be the most important functional group.     

Chemical constituents from Abrus cantoniensis and their cytotoxic effects on cancer cells

Two new compounds named 4-(4-hydroxybenzyl)-isofraxidin (1) and 1''-methoxyl-bavacoumestan B (2), along with five known compounds (3–7) were isolated from the EtOAc-soluble extract of Abrus cantoniensis. Their structures were elucidated with spectroscopic and physico-chemical analyses. All isolates were evaluated for their cytotoxic activities against four cancer cell lines including HepG2, SMMC-7721, A549 and MCF-7. Among them, compounds 1 and 5 exhibited significant cytotoxic activity on the above four cell lines. In particular, 1 showed the potent cytotoxic activity on HepG2 and SMMC-7721 cells with IC₅₀ values of 4.31 ± 0.5 and 3.24 ± 0.9 μM, respectively.     

Six new dihydrobenzofuran lignans from the branches and leaves of Illicium wardii and their cytotoxic activities

Six new dihydrobenzofuran lignans, named illiciumlignans A⿿F (compounds 1⿿6), along with 15 known compounds (7⿿21) were isolated from the branches and leaves of Illicium wardii. The structures of 1⿿6 were determined using a combination of 1D and 2D NMR, HR-ESI⿿-MS, and CD spectroscopic data. Illiciumlignan D (4) is the first reported dihydrobenzofuran lignan arabinofuranoside that is derivatized with the arabinofuranose moiety on C-9⿲. Compounds 1⿿21 were evaluated for cytotoxic activity against four human cancer cell lines. Compounds 8, 12 and 20 exhibited significant activity against human cancer cell lines (A549, SKOV3, HepG2 and HCT116), with IC₅₀ values ranging from 2.7 to 14.9 μM.     

Steroidal alkaloids from Solanum erianthum and their anti-breast cancer properties

Two new glycoalkaloids, erianosides A (1) and B (2) along with five known compounds (3–7) were isolated from the leaves of Solanum erianthum. Their structures were elucidated from analyses of spectroscopic data and all isolates were tested for in vitro cytotoxic activity against human breast cancer cell lines (BT-549, MDA-MB-231, T74D, and MCF-7). Solasonine (5) and solamargine (6) were active against the aforementioned four cancer cell lines with IC₅₀ values of 27.26–35.89 and 5.84–10.13 μM, respectively. Erianoside A (1) (T74D: IC₅₀, 56.39 µM) and solasodine (3) (BT-549 and MDA-MB-231: IC₅₀, 59.15 and 75.63 µM, respectively) had moderate cytotoxic effects towards some cell lines in the panel.     

Design,synthesis and biological evaluation of novel 1,3,4-trisubstituted pyrazole derivatives as potential chemotherapeutic agents for hepatocellular carcinoma

A series of novel 1,3,4-trisubstituted pyrazole derivatives were synthesized and evaluated for their cytotoxic activity against three different cancer cell lines namely HCT116, UO-31 and HepG2. Compounds 3b, 3d, 7b and 9 showed excellent anticancer activity against all the tested cancer cell lines and had better cytotoxic activities than the reference drug, Sorafenib. Therefore, these compounds were chosen to be further evaluated in a panel of HCC cell lines. Among them, 3b and 7b were the most active compounds against HCC cells used here. Further studies on the mechanism demonstrated that 3b and 7b induced apoptosis in addition to induction of cell cycle arrest at G2/M phase in HepG2 and Huh7 cells. Consistent with these results, caspase-3 assay was done and the results revealed that the pro-apoptotic activity of the target compounds could be due to the stimulation of caspases-3. In addition, CDK1 inhibition assay was done and it was found that compounds 3b and 7b inhibited CDK1 activities with IC₅₀ values of 2.38 and 1.52 µM, respectively. Finally, pyrazole derivatives 3b and 7b showed potent bioactivities, indicating that these compounds could be potent anticancer drugs in the future.     

Two novel neo-clerodane diterpenoids from Scutellaria barbata

Two novel neo-clerodane diterpenoids, barbatellarines A (1) and B (2), were isolated from the whole plants of Scutellaria barbata, along with the known compound scutebarbatine F (3). The chemical structures and relative stereochemistry of the isolated compounds were established by NMR (1D and 2D) and mass spectroscopic analyses. Compounds 2 and 3 were evaluated for in vitro cytotoxic activity against the HL-60 (human leukemia), MCF7 (human breast cancer), and LLC (Lewis lung carcinoma) cancer cell lines. Compound 2 exhibited weak cytotoxic activity against HL-60 cells, with an IC₅₀ value of 41.4 μΜ.     

Two new lactones from whole herbs of Patrinia villosa Juss

Chemical investigation of 70% EtOH exact of Patrinia villosa Juss. led to the isolation, purification and identification of two new lactones (1-2) along with twelve known compounds (3-14). Their structures were established by comprehensive spectroscopic analyses. All compounds were evaluated for their cytotoxic activities against A549, HepG2, Hep3 B and MCF-7 cancer cell lines. Compounds 1, 8, 10, 11 and 12 displayed weak cytotoxic activities against MCF-7 cell line. In addition, compounds 1, 2, 8, 10, 11 and 12 were also tested their antimicrobial activities against Micrococcus luteus. Unfortunately, these compounds were found to be inactive.     

Discovery of novel 4(1H)-quinolone derivatives as potential antiproliferative and apoptosis inducing agents

A series of novel 4(1H)-quinolone derivatives was synthesized and evaluated for antiproliferative activity in vitro. The results showed that these compounds exhibited more potent antiproliferative effect against a panel of human tumor cell lines than the lead compound 7-chloro-4(1H)-quinolone 1. Compound 7e was found to be the most potent antiproliferative agent and to exhibit selective cytotoxic activity against HepG2 cell lines with IC₅₀ value lower than 1.0 μM. Annexin V/FITC-PI assay showed that compound 7e induced apoptosis in HepG2 cells with a dose-dependent manner. Western blotting analysis indicated that compound 7e induced cell cycle arrest in G2/M phase by p53-depedent pathway.     

New tirucallane triterpenoids from Picrasma quassioides with their potential antiproliferative activities on hepatoma cells

Seven new tirucallane-type triterpenoids (1–7), kumuquassin A-G, along with 20 known analogues (8–27) were isolated from the stems of Picrasma quassioides. The structures and the absolute configurations of new compounds were elucidated by spectroscopic data, electronic circular dichroism (ECD) spectroscopic analyses and quantum ECD calculations. Notably, kumuquassin A (1) contains a rare Δ^{17, 20} double bond, kumuquassin B (2) is the first example of tirucallane triterpenoid possessing a 5/3 biheterocyclic ring system at the side chain. All the compounds were screened for the cytotoxicity against two human hepatoma cell lines, HepG2 and Hep3B, and several compounds exhibited promising activity. The most potential compound 3 was selected for cell cycle analysis, which showed that 3 could cause an accumulation of HepG2 cells at subG1 peak. Annexin V-FITC/PI staining further confirmed that compound 3 caused death of hepatoma cells through apoptosis induction.     

Cytotoxic polyhydroxy serratene triterpenoids from Lycopodium complanatum

Phytochemical investigation of the 70% aqueous EtOH extract of Lycopodium complanatum led to six new polyhydroxy serratene triterpenoids (serrat A-F, 1–6), along with a known analogue (7). Their structures and configurations were elucidated by data analysis of HRESIMS, 1D and 2D NMR, in combination with comparisons of reported experimental spectroscopic data. All the isolates were evaluated cytotoxic activities against HepG2 cells, MCF-7 cells and series human lung cancer cell lines A549, Calu-6, NCI-H441, NCI-H226 and NCI-H1975. The results indicated that certain compounds inhibited proliferation of human cancer cells. Moreover, all compounds possessed selective cytotoxic activities on MCF-7 cells. Further, possible biosynthesis pathways of these compounds were proposed.     

Synthesis and anticancer activity of a novel series of 9-O-substituted berberine derivatives: A lipophilic substitute role

To alter its hydrophobicity, a series of compounds bearing 9-O-alkyl- or 9-O-terpenyl- substituted berberine were synthesized and evaluated for anticancer activity against human cancer HepG2 and HT29 cell lines. We found that the lipophilic substitute of 9-O-alkyl- and 9-O-terpenyl berberine derivatives plays a role in inhibiting the human cancer cell growth and its activity could be maximized with the optimized substitute type and chain length. Most strikingly, nonetheless, of the six compounds prepared, sample 8, a farnesyl 9-O-substituted berberine, showed either comparable or better cytotoxic activity against human cancer HepG2 cell line than that of berberine. Compound 8 had also shown a 104-fold antiproliferation activity in compare with berberine against human hepatoma HepG2 cell lines after 48 incubation hours. Further, in Hoechst 33258 and annexin V-FITC/PI staining analyses it induced apoptosis in HepG2 cells at lower concentration than that of berberine for 24 h. Take all; farnesyl 9-O-substituted berberine could be a potential candidate for new anticancer drug development.     

Design,synthesis and evaluation of novel hybrids between 4-anilinoquinazolines and substituted triazoles as potent cytotoxic agents

In this research several series of novel dioxygenated ring fused 4-anilinoquinazolines (10a-d) and 4-anilinoquinazoline-substituted triazole hybrid compounds (11–14) have been designed and synthesized. Their biological significance was highlighted by evaluating in vitro for anticancer activities, wherein several compounds displayed excellent activity specifically against three human cancer cell lines (KB, epidermoid carcinoma; HepG2, hepatoma carcinoma; SK-Lu-1, non-small lung cancer). Especially, compound 13a exhibited up to 100-fold higher cytotoxicity in comparison with erlotinib. Docking the most cytotoxic compounds (11d, 13a, 13b, and 14c) into the ATP binding site of different EGFR tyrosine kinase domains was perfomed to predict the analogous binding mode of these compounds to the EGFR targets.     

Cytotoxic triterpene diglycosides from the sea cucumber Stichopus horrens

Using various chromatographic separation techniques, eight triterpene diglycosides (1–8), including four new compounds namely stichorrenosides A–D (1–4), were isolated from a methanol extract of the Vietnamese sea cucumber S. horrens. Their structures were elucidated based on spectroscopic analyses, including HR ESI MS, 1D and 2D NMR. Their in vitro cytotoxic activity against five human cancer cell lines, Hep-G2 (hepatoma cancer), KB (epidermoid carcinoma), LNCaP (prostate cancer), MCF7 (breast cancer), and SK-Mel2 (melanoma), was evaluated using SRB methods. Stichorrenoside D (4), stichoposide A (5), and 3β-O-[β-d-xylopyranosyl-(1→2)-β-d-xylopyranosyl]-23S-acetoxyholost-7-ene (7) showed strong cytotoxicity on all five tested cancer cell lines, whereas significant effect was observed for stichorrenoside C (3) and stichoposide B (6).     

Steroidal saponins with cytotoxic activities from the rhizomes of Anemarrhena asphodeloids Bge.

Two new steroidal saponins, named timosaponin R (1) and S (2), together with seven known compounds (3-9) were isolated from the rhizomes of Anemarrhena asphodeloides Bge. Their structures were elucidated on the basis of NMR spectroscopy and mass spectrometry. All the compounds were evaluated for cytotoxic activities against the four human cancer cell lines MCF7, SW480, HepG2 and SGC7901 in vitro. Compounds 7-9 showed moderate activities against all the cell lines.     

Design,synthesis, 3D pharmacophore,QSAR, and docking studies of carboxylic acid derivatives as Histone Deacetylase inhibitors and cytotoxic agents

In this study, five series of (E)-6-(4-substituted phenyl)-4-oxohex-5-enoic acids IIb–f (E), (E)-3-(4-(substituted)-phenyl)acrylic acids IIIa–g (E), 4-(4-(substituted)phenylamino)-4-oxobutanoic acids VIa,b,e, 5-(4-(substituted)phenylamino)-5-oxopentanoic acids VIIa,f and 2-[(4-(substituted)phenyl) carbamoyl]benzoic acids VIIIa,e were designed and synthesized. Selected compounds were screened in vitro for their cytotoxic effect on 60 human NCI tumor cell lines. Compound IIf (E) displayed significant inhibitory activity against NCI Non-Small Cell Lung A549/ATCC Cancer cell line (68% inhibition) and NCI-H460 Cancer cell line (66% inhibition). Moreover, the final compounds were evaluated in vitro for their cytotoxic activity on HepG2 Cancer cell line in which histone deacetylase (HDAC) is overexpressed. Compounds IIc (E), IIf (E), IIIb (E), and IIIg (E) exhibited the highest cytotoxic activity against HepG2 human cancer cell lines with IC₅₀ ranging from 2.27 to 10.71 μM. In addition, selected compounds were tested on histone deacetylase isoforms (HDAC1–11). Molecular docking simulation was also carried out for HDLP enzyme to investigate their HDAC binding affinity. In addition, generation of 3D-pharmacophore model and quantitative structure activity relationship (QSAR) models were combined to explore the structural requirements controlling the observed cytotoxic properties.     

Chemical constituents of Ligularia alticola Worosch. leaves and their biological activities

Seven eremophilane-type sesquiterpenes (1–7), six cycloartane derivatives (8–13) and α-amyrin acetate (14) were isolated from the leaves of the far-eastern plant Ligularia alticola Worosch. (Family Asteraceae). (4S,5R,8S,10R)-8-Ethoxyeremophil-7(11)-en-12(8)-olide (1), 8α,11-epidioxy-8β-methoxyeremophil-6-ene (2) and 29-norcycloartan-3α-ol (8) have not been previously reported. Fukinone α-epoxide (3) was isolated for the first time from a natural source. The structures of all the compounds were established by the extensive analysis of their 1D and 2D NMR spectra and HR ESI mass spectrometry. The absolute stereochemistry of 1 was determined by comparison of theoretical and experimental ECD spectra with the application of B3LYP-TDDFT and B3LYP-GIAO calculations as well as by NMR spectroscopy. Compound 1 showed cytotoxic action against human cancer HL-60, Raji, and THP-1 cell lines (IC₅₀ 12.6, 6.0 and 6.9 μM, respectively). Compounds 2 and 4 demonstrated significant cytotoxic activities against HL-60 (IC₅₀ 2.8 and 5.8 μM, respectively) and Raji cells (IC₅₀ 2.9 and 4.2 μM, respectively). Compound 6 was cytotoxic against Raji cells (IC₅₀ 4.6 μM). None of tested compounds were cytotoxic against RAW 264.7 cells. Compounds 1 and 4–7 significantly decreased intracellular ROS levels, induced by endotoxic LPS from Escherichia coli in RAW 264.7 murine macrophages.