scholarly journals New Alkoxy Flavone Derivatives Targeting Caspases: Synthesis and Antitumor Activity Evaluation

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 129 ◽  
Author(s):  
Joana Moreira ◽  
Diana Ribeiro ◽  
Patrícia Silva ◽  
Nair Nazareth ◽  
Madalena Monteiro ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Inhibitory Activity ◽  
Alkyl Halide ◽  
Human Tumor ◽  
Inhibitory Effect ◽  
Synthetic Approach ◽  
Growth Inhibitory Effect ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Caspase 7

The antitumor activity of natural flavonoids has been exhaustively reported. Previously it has been demonstrated that prenylation of flavonoids allows the discovery of new compounds with improved antitumor activity through the activation of caspase-7 activity. The synthesis of twenty-five flavonoids (4–28) with one or more alkyl side chains was carried out. The synthetic approach was based on the reaction with alkyl halide in alkaline medium by microwave (MW) irradiation. The in vitro cell growth inhibitory activity of synthesized compounds was investigated in three human tumor cell lines. Among the tested compounds, derivatives 6, 7, 9, 11, 13, 15, 17, and 18 revealed potent growth inhibitory activity (GI50 < 10 μM), being the growth inhibitory effect of compound 13 related with a pronounced caspase-7 activation on MCF-7 breast cancer cells and yeasts expressing human caspase-7. A quantitative structure-activity relationship (QSAR) model predicted that hydrophilicity, pattern of ring substitution/shape, and presence of partial negative charged atoms were the descriptors implied in the growth inhibitory effect of synthesized compounds. Docking studies on procaspase-7 allowed predicting the binding of compound 13 to the allosteric site of procaspase-7.

scholarly journals Norhierridin B, a New Hierridin B-Based Hydroquinone with Improved Antiproliferative Activity

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1578
Author(s):  
Pedro Brandão ◽  
Joana Moreira ◽  
Joana Almeida ◽  
Nair Nazareth ◽  
Ivo E. Sampaio-Dias ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Human Tumor ◽  
Colon Adenocarcinoma ◽  
Inhibitory Effect ◽  
Growth Inhibitory Effect ◽  
Protein Levels ◽  
Cycle Arrest ◽  
Growth Inhibitory ◽  
Potent Growth

Hierridin B (6), a methylated hydroquinone isolated from the marine picocyanobacterium Cyanobium sp. LEGE 06113, moderately inhibited the growth of colon adenocarcinoma HT-29 cells. Aiming to improve the potential antitumor activity of this natural product, the demethylated analogue, norhierridin B (10), as well as its structurally-related quinone (9), were synthesized and evaluated for their growth inhibitory effect on a panel of human tumor cell lines, including the triple-negative breast cancer (TNBC) cells MDA-MB-231, SKBR3, and MDA-MB-468. Norhierridin B (10) showed a potent growth inhibitory effect on all cancer cell lines. Moreover, the growth inhibitory effect of compound 10 on MDA-MB-231 cells was associated with cell cycle arrest and apoptosis. Norhierridin B (10) interfered with several p53 transcriptional targets, increasing p21, Bax, and MDM2, while decreasing Bcl-2 protein levels, which suggested the potential activation of a p53 pathway. Altogether, these results evidenced a great improvement of the antitumor activity of hydroquinone 10 when compared to 6 and its structurally-related quinone (9). Notably, hydroquinone 10 displayed a prominent growth inhibitory activity against TNBC cells, which are characterized by high therapeutic resistance.

Natural Compounds with Cell Growth Inhibitory Activity in Human Tumor Cell Lines

2013 ◽  
Vol 13 (10) ◽  
pp. 1582-1589 ◽  
Author(s):  
Cristiane Cazal ◽  
Kantima Choosang ◽  
Vanessa Severino ◽  
João Fernandes ◽  
Maria Silva ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity

scholarly journals The inhibition of growth by chemical compounds

1942 ◽  
Vol 130 (860) ◽  
pp. 255-299 ◽  
Keyword(s):  
Inhibitory Activity ◽  
Inhibitory Effect ◽  
Biological Properties ◽  
Usual Sense ◽  
Carcinogenic Activity ◽  
Related Substances ◽  
Inhibition Of Growth ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Derivatives Of

In an extended investigation of the growth-inhibitory activity of carcinogenic compounds and related substances, over two hundred compounds were tested, including various 5-, 10- and 9 : 10-substituted benzanthracenes, dimethyl derivatives of anthracene, nitrogenous analogues of 1 : 2-benzanthracene, benzphenothiazines and dibenzphenothiazines, compounds related to 3 : 4-benzphenanthrene, dibenzfluorenes, dibenzcarbazoles, dibenzpyrenes, azonaphthalenes and related products, naphthylam ines and naphthaquinones, arsenonaphthalenes, derivatives of triphenylethylene, and diphenyl derivatives of indene, β -naphthindole and β -naphthofuran. A striking degree of correspondence was often shown by the inhibitory and carcinogenic activity of closely related com pounds (e. g. 5-alkyl benzanthracenes; dibenzfluorenes; dibenzphenanthrenes; 2 : 2'-azonaphthalene, 2 : 2'-diamino -1 : 1'-dinaphthyl and 3 : 4 : 5 : 6-dibenzcarbazole). However, no inhibitory activity was observed for certain carcinogenic 10- and 9 : 10- substituted benzanthracenes. On the other hand, inhibitory activity was noted in a few compounds (e. g. 1 : 2'-azonaphthalene) which have yielded few or no tum ours in exhaustive tests, and in some of a group of synthetic oestrogenic compounds which, although not carcinogenic in the usual sense, are nevertheless associated with the induction of individual types of tum our under special conditions. The relation between molecular structure and inhibitory activity depends in general upon an optimal degree of molecular complexity and upon certain more specific requirements. Nevertheless, the results obtained with derivatives of triphenylethylene suggest that inhibitory activity may still be shown by compounds diverging widely from the polycyclic structure and possessing only a skeletal resemblance. Diminution of inhibitory effect with increased substituent size was shown in the 5-alkyl benzanthracenes tested, although the same relation does not necessarily obtain for other positions. The influence of the nature of the substituent is seen (for example) in the contrast between 10-methyl-, 10-amino- and 10-cyano-l: 2-benzanthracene (inhibitory) and 10-isopropyl - 1:2-benzanthracene (inactive). Lastly, numerous experiments indicated that solubilization of an active compound usually entails decrease of activity, although certain apparent exceptions were encountered. In addition to the relationship between inhibitory activity and carcinogenicity, and that between both biological properties and chemical structure, consideration is also given to the mode of production of the inhibitory effect.

scholarly journals Growth control in cultured 3T3 fibroblasts. Assays of cell proliferation and demonstration of a growth inhibitory activity.

1979 ◽  
Vol 83 (3) ◽  
pp. 562-575 ◽  
Author(s):  
P A Steck ◽  
P G Voss ◽  
J L Wang
Keyword(s):  
Cell Proliferation ◽  
Inhibitory Activity ◽  
Gel Filtration ◽  
Growth Control ◽  
Inhibitory Effect ◽  
Cell Number ◽  
Target Cells ◽  
Similar Treatment ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity

Treatment of sparse, proliferating cultures of 3T3 cells (target cells) with medium conditioned by exposure to density-inhibited 3T3 cultures resulted in an inhibition of growth and division in the target cells when compared to similar treatment with unconditioned medium (UCM). This differential effect of conditioned medium (CM) and UCM on target cells was demonstrated using three assay systems: (a) assessment of total cell number; (b) measurement of [3H]thymidine incorporated into acid-precipitable DNA; and (c) determination of the percentage of radioactively labeled nuclei in individual cells after incorporation of [3H]thymidine. The difference in the total incorporation of [3H]thymidine in CM-treated and UCM-treated cells was reflected by a difference in the percent of labeled cells. There was no differences in the average number of grains per labeled cell in the two cultures. Moreover, the inhibitory effect of the CM on target cell proliferation was reversible. Finally, this growth inhibitory activity can be collected in serum-free medium, precipitated by ammonium sulfate, and fractionated by gel filtration. In these purification procedures, the inhibitory activity was consistently found to be associated with the protein-containing fractions of the CM. No activity was found upon similar treatment with UCM. These results suggest that a system has been developed for the purification and molecular analysis of growth inhibitory factors that may mediate growth control in culture fibroblasts.

scholarly journals AURUM POLYACRYLATE: THE EXPERIMENTAL STUDY OF THE ANTITUMOR ACTIVITY

2020 ◽  
Vol 19 (4) ◽  
pp. 74-85
Author(s):  
L. A. Ostrovskaya ◽  
D. B. Korman ◽  
N. V. Bluhterova ◽  
M. M. Fomina ◽  
V. A. Rikova ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Lung Carcinoma ◽  
Human Tumor ◽  
Inhibitory Effect ◽  
Lewis Lung ◽  
Human Tumor Cells ◽  
Growth Inhibitory Effect ◽  
Growth Inhibitory ◽  
Mcf 7 ◽  
Potential Antitumor

Introduction. The investigation of metal substituted organic compounds as potential antitumor drugs is one of the promising areas of research in experimental and clinical oncology.Objective. The pre-clinical study of the original antitumor drug aurum polyacrylate (aurumacryl) which belongs to such new for oncology group of compounds as polyacrylates of metals was the aim of this work.Materials and methods.  Aurumacryl antitumor activity was determined as the tumor growth inhibitory effect against some of the murine solid tumors (Lewis lung carcinoma, Acatol adenocarcinoma and Ca-755 adenocarcinoma). Drug cytotoxic effect against some of the human tumor cells (Mel-Mo melanoma, A549 lung carcinoma, MCF-7 breast carcinoma, HCT116 colon adenocarcinoma) was evaluated with standard МТТ-test. The aurumacryl pharmacokinetics in tumor bearing mice (Lewis lung carcinoma) was studied. The inductively coupled plasma mass spectrometry method was used for the estimation of the aurum maintenance in the tested tissues (tumor, blood, kidneys, liver, lungs, spleen, brain).Results. The 80–90 % tumor growth inhibitory effect of aurumacryl against some solid tumors in mice had been revealed in vivo as well as the death of the 60–90 % human tumor cells of various origins in vitro. Beside this the strong decrease of the number of proliferating MCF-7 tumor cells had been shown. The distribution of aurumacryl in the body of the mice with the solid tumor had been revealed.Conclusion. On the base of the data obtained the further study of the aurumacryl as a potential antitumor agent seems rather promising.

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