Cytotoxic effect of euphol from Euphorbia tirucalli on a large panel of human cancer cell lines.

e13557 Background: The tetracyclic triterpene alcohol euphol is the main constituent found in the sap of Euphorbia tirucalli. In Brazil its latex is used as anticancer and other diseaseas folk treatment, yet, little is known about its anticancer proprieties. We aimed to study the antitumor effect of euphol on a large panel of human cancer cell lines. Methods: Anti-tumor effects of euphol in vitro were assessed using MTS assays on 77 human cancer lines from13 solid tumor models, such as breast, colon, bladder, prostate, lung, pancreas, esophagus, glioblastoma, melanoma, head and neck and cervical cancer. Additionally, we evaluate the its potential combinatorial value with temozolomide in gliomas. Ongoing experiments will identify potential drug target(s) by assessing changes in global protein expression. Results: Euphol exhibited dose and time-dependent cytotoxic effects on all cancer cell lines analyzed. Among each tumor type, the distinct cell line exhibited a heterogeneous profile of response to euphol. Esophageal squamous cell carcinoma and pancreatic carcinomas showed the most sensitive profile. In comparison with temozolomide, euphol showed a median of 30 fold higher efficacy, range 5-167 fold, in the glioma cell lines analyzed (Table). Conclusions: Euphol demonstrated potent anti-tumor activity on the majority of cancer cell lines evaluated. Our findings may provide insight into the tailoring designing of euphol-based therapies for cancer patients. [Table: see text]

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Cytotoxic activity of semi-synthetic ingenol derived from Euphorbia tirucalli on a large panel of human cancer cell lines.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e13559 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e13559-e13559

Author(s):

Viviane Aline Oliveira Silva ◽

Marcela Nunes Rosa ◽

Aline Tansini ◽

Joao Paulo Da S.N. Lima ◽

Chris Jones ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Human Cancer Cell Lines ◽

Euphorbia Tirucalli ◽

Large Panel ◽

Anti Tumor Activity

e13559 Background: The latex from Euphorbia tirucalli is used in Brazil as anticancer and other disease as folk treatment; however, little is known about its anticancer proprieties. We report in vitro activity of 3 semi-synthetic ingenol compounds derived from E. tirucalli, ingenol A (ingenol-3-trans-cinnamate), ingenol B (3-caproyl-ingenol) and ingenol C (ingenol-3-dodecanoate), against a large panel of human cancer cell lines. Methods: Anti-tumor effects of the 3 semi-synthetic compounds were assessed using MTS assays on 77 cancer lines from 13 tumor models, such as breast, colon, bladder, prostate, lung, pancreas, esophagus, glioblastoma, melanoma, head and neck and cervical cancer. Additionally, we evaluate the its potential combinatorial value with temozolomide (TMZ) in gliomas. Ongoing experiments will identify potential drug target(s) by assessing changes in global protein expression. Results: Ingenol A, B and C exhibited dose-dependent and time-dependent cytotoxic effects. Amongst the derived tested, ingenol C displayed the best activity across the tumor cell lines. In comparison with TMZ, ingenol C showed a median of 136 fold higher efficacy, range 15-511 fold, in the glioma cell lines analyzed. Conclusions: The semi-synthetic ingenol compounds, in particular the ingenol C, demonstrated a potent anti-tumor activity on all cancer cell lines evaluated. Our findings may provide insight into designing ingenol-based therapies for cancer patients. [Table: see text]

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Modified ingenol semi-synthetic derivatives from Euphorbia tirucalli induce cytotoxicity on a large panel of human cancer cell lines

Investigational New Drugs ◽

10.1007/s10637-019-00728-0 ◽

2019 ◽

Vol 37 (5) ◽

pp. 1029-1035 ◽

Cited By ~ 1

Author(s):

Viviane A. O Silva ◽

Marcela N. Rosa ◽

Olga Martinho ◽

Amilcar Tanuri ◽

João Paulo Lima ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Human Cancer Cell Lines ◽

Euphorbia Tirucalli ◽

Large Panel ◽

Synthetic Derivatives

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Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity

Molecules ◽

10.3390/molecules26133923 ◽

2021 ◽

Vol 26 (13) ◽

pp. 3923

Author(s):

Adel A.-H. Abdel-Rahman ◽

Amira K. F. Shaban ◽

Ibrahim F. Nassar ◽

Dina S. EL-Kady ◽

Nasser S. M. Ismail ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Molecular Docking Study ◽

Human Cancer Cell Lines ◽

Hct 116 ◽

Mcf 7

New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (1). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine-−C2 functionalized derivatives. The derived pyrazolpyridine-N-glycosides were synthesized via heterocyclization of the C2-thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative 14 and the tricyclic pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine 15 were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone 1, 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (4), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (8), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (11), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate (14) are among the most active inhibitors with IC50 values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC50 0.394 μM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC50 ranges of 31.3–49.0, 19.3–55.5, 22.7–44.8, and 36.8–70.7 μM, respectively compared to doxorubicin (IC50 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.

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