scholarly journals Synthesis and Evaluation of Anticancer Activities of Novel C-28 Guanidine-Functionalized Triterpene Acid Derivatives

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 3000 ◽  
Author(s):  
Anna Spivak ◽  
Rezeda Khalitova ◽  
Darya Nedopekina ◽  
Lilya Dzhemileva ◽  
Milyausha Yunusbaeva ◽  
...  
Keyword(s):  
Human Fibroblasts ◽  
Human Tumor ◽  
Jurkat Cells ◽  
Anticancer Activities ◽  
Triterpene Acid ◽  
Guanidine Group ◽  
Triterpene Acids ◽  
Cycle Arrest ◽  
Normal Human ◽  
Derivatives Of

Triterpene acids, namely, 20,29-dihydrobetulinic acid (BA), ursolic acid (UA) and oleanolic acid (OA) were converted into C-28-amino-functionalized triterpenoids 4–7, 8a, 15, 18 and 20. These compounds served as precursors for the synthesis of novel guanidine-functionalized triterpene acid derivatives 9b–12b, 15c, 18c and 20c. The influence of the guanidine group on the antitumor properties of triterpenoids was investigated. The cytotoxicity was tested on five human tumor cell lines (Jurkat, K562, U937, HEK, and Hela), and compared with the tests on normal human fibroblasts. The antitumor activities of the most tested guanidine derivatives was lower, than that of corresponding amines, but triterpenoids with the guanidine group were less toxic towards human fibroblasts. The introduction of the tris(hydroxymethyl)aminomethane moiety into the molecules of triterpene acids markedly enhanced the cytotoxic activity of the resulting conjugates 15, 15c, 18b,c and 20b,c irrespective of the triterpene skeleton type. The dihydrobetulinic acid amine 15, its guanidinium derivative 15c and guanidinium derivatives of ursolic and oleanolic acids 18c and 20c were selected for extended biological investigations in Jurkat cells, which demonstrated that the antitumor activity of these compounds is mediated by induction of cell cycle arrest at the S-phase and apoptosis.

scholarly journals The selective toxic effect of dialdehyde derivatives of the pyrimidine nucleosides on human tumor cells

2015 ◽  
Vol 61 (4) ◽  
pp. 497-502 ◽  
Author(s):  
A.S. Efremova ◽  
S.I. Shram ◽  
M.S. Drenichev ◽  
G.A. Posypanova ◽  
N.F. Myasoedov ◽  
...  
Keyword(s):  
Toxic Effect ◽  
Tumor Cells ◽  
Human Fibroblasts ◽  
Human Tumor ◽  
Lung Fibroblasts ◽  
Growth And Survival ◽  
Cultured Human Fibroblasts ◽  
Normal Human ◽  
The Impact ◽  
Derivatives Of

The impact of a number of synthetic nucleoside derivatives on the growth and survival of cultured human ovarian tumor cells (line SKOV-3) and normal human lung fibroblasts was investigated. It was shown that the dialdehyde derivatives of uridine, 1--D-eritrofuranozyl uracil and 3-O--D-ribofuranosyl-2-deoxythymidine, in contrast to their unoxidized counterparts, exert marked toxic effect on SKOV-3 cells. Cultured human fibroblasts were less susceptible to the damaging effect of the dialdehyde nucleosides. The dialdehyde derivative of 1--D-eritrofuranozyl uracil demonstrated greatest differences in the cytotoxic effect on these cultures: inhibition of tumor SKOV-3 cells growth on 50% or more was achieved at the concentrations of this compound ten times lower than in the case of normal fibroblasts.

scholarly journals Design, Synthesis, and Structural Characterization of Novel Diazaphenothiazines with 1,2,3-Triazole Substituents as Promising Antiproliferative Agents

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4388 ◽  
Author(s):  
Morak-Młodawska ◽  
Pluta ◽  
Latocha ◽  
Jeleń ◽  
Kuśmierz
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Human Fibroblasts ◽  
Human Tumor ◽  
Design Synthesis ◽  
Human Tumor Cell Lines ◽  
Ic50 Values ◽  
Normal Human ◽  
Low Cytotoxicity

A series of novel 1,2,3-triazole-diazphenothiazine hybrids was designed, synthesized, and evaluated for anticancer activity against four selected human tumor cell lines (SNB-19, Caco-2, A549, and MDA-MB231). The majority of the synthesized compounds exhibited significant potent activity against the investigated cell lines. Among them, compounds 1d and 4c showed excellent broad spectrum anticancer activity, with IC50 values ranging from 0.25 to 4.66 μM and 0.25 to 6.25 μM, respectively. The most promising compound 1d, possessing low cytotoxicity against normal human fibroblasts NHFF, was used for gene expression analysis using reverse transcription–quantitative real-time PCR (RT–qPCR). The expression of H3, TP53, CDKN1A, BCL-2, and BAX genes revealed that these compounds inhibited the proliferation in all cells (H3) and activated mitochondrial events of apoptosis (BAX/BCL-2).

Cell cycle arrest and aberration yield in normal human fibroblasts. I. Effects of X‐rays and 195 MeV u−1C ions

2004 ◽  
Vol 80 (9) ◽  
pp. 621-634 ◽  
Author(s):  
E. Nasonova ◽  
K. Füssel ◽  
S. Berger ◽  
E. Gudowska‐Nowak ◽  
S. Ritter
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Human Fibroblasts ◽  
X Rays ◽  
Cycle Arrest ◽  
Normal Human ◽  
Aberration Yield

scholarly journals Study of the Anti-Proliferative Activity of 5-Substituted 4,7-Dimethoxy-1,3-Benzodioxole Derivatives of SY-1 fromAntrodia camphorataon Human COLO 205 Colon Cancer Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Hsiu-Man Lien ◽  
Po-Tsun Kuo ◽  
Chao-Lu Huang ◽  
Jung-Yie Kao ◽  
Ho Lin ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Carcinoma Cells ◽  
Flow Cytometry Analysis ◽  
Antrodia Camphorata ◽  
Cycle Arrest ◽  
Normal Human ◽  
G1 Cell Cycle Arrest ◽  
Derivatives Of ◽  
Potent Inhibitory Activity

A set of 10 4,7-dimethoxy-1,3-benzodioxole derivatives based on a lead compound previously discovered by our group, SY-1, which was isolated fromAntrodia camphorata, were evaluated for theirin vitroinhibitory activity on human colorectal carcinoma cells (COLO 205). Structure-activity relationship studies of the 10 compounds indicated the importance of the chain length of the alkyl group at the 5-position, and the 2-propenyl substituent named “apiole” exhibited the most potent inhibitory activity. In the present study, we demonstrate that the SY-1 analogue “apiole” decreased the proliferation of COLO 205 cells, but not that of normal human colonic epithelial cells (FHC). The G0/G1 cell cycle arrest induced by apiole (75–225 μM) was associated with significantly increased levels of p53, p21 and p27 and decreased levels of cyclin D1. Concerning COLO 205 cell apoptosis, apiole (>150 μM) treatment significantly increased the levels of cleaved caspases 3, 8, 9 and bax/bcl-2 ratio and induced ladder formation in DNA fragmentation assay and sub-G1 peak in flow cytometry analysis. These findings suggest that apiole can suppress COLO 205 cell growth; however, the detailed mechanisms of these processes require further investigation.

Clonal variation of cadmium response in human tumor cell lines

1986 ◽  
Vol 250 (2) ◽  
pp. C256-C263 ◽  
Author(s):  
M. D. Enger ◽  
J. G. Tesmer ◽  
G. L. Travis ◽  
S. S. Barham
Keyword(s):  
Cell Lines ◽  
Human Fibroblasts ◽  
Human Tumor ◽  
Clonal Variation ◽  
Parental Line ◽  
Early Passage ◽  
Normal Human ◽  
Dna Histograms

Subpopulations of human tumor-derived cell lines A101D, A204, and A549 were screened for Cd2+ cytotoxic response. Three of six A549, two of seven A101D, and four of seven A204 subpopulations were found to differ significantly from the parental line. A variant subpopulation of A101D (T3) was shown by flow cytometry to be comprised of cells having two distinct DNA histograms. One histogram, type 1, resembles that of normal human fibroblasts. The other, type 2, represents cells with one-third more DNA. Early passage T3 clonal populations were comprised primarily of type 1 cells. With passage, type 1 cells decreased relative to type 2 so that by passage 47 the culture was predominantly type 2. Correspondingly, the A101D T3 subpopulation became more Cd2+ sensitive with time in culture. Subclones having only type 1 DNA histograms were found to be Cd2+ resistant relative to subclones with type 2 histograms, and treatment of A101D T3 cultures having approximately equal amounts of type 1 and 2 cells with 2 microM Cd2+ resulted in the selection of type 1 cells. The enhanced Cd2+ resistance phenotype shown by A101D T3 type 1 cells correlated with reduced Cd2+ uptake and is not attributable to enhanced metallothionein synthesis.

Animal Venoms have Potential to Treat Cancer

2019 ◽  
Vol 18 (30) ◽  
pp. 2555-2566 ◽  
Author(s):  
Bhaswati Chatterjee
Keyword(s):  
Cancer Therapeutics ◽  
Sea Anemones ◽  
Anticancer Activities ◽  
Inhibition Of Proliferation ◽  
Cycle Arrest ◽  
Venomous Animals ◽  
Anti Cancer ◽  
Cancerous Cells ◽  
Animal Venoms ◽  
Proteins And Peptides

The resistance to chemotherapeutics by the cancerous cells has made its treatment more complicated. Animal venoms have emerged as an alternative strategy for anti-cancer therapeutics. Animal venoms are cocktails of complex bioactive chemicals mainly disulfide-rich proteins and peptides with diverse pharmacological actions. The components of venoms are specific, stable, and potent and have the ability to modify their molecular targets thus making them good therapeutics candidates. The isolation of cancer-specific components from animal venoms is one of the exciting strategies in anti-cancer research. This review highlights the identified venom peptides and proteins from different venomous animals like snakes, scorpions, spiders, bees, wasps, snails, toads, frogs and sea anemones and their anticancer activities including inhibition of proliferation of cancer cells, their invasion, cell cycle arrest, induction of apoptosis and the identification of involved signaling pathways.

scholarly journals Precursor-Boosted Production of Metabolites in Nasturtium officinale Microshoots Grown in Plantform Bioreactors, and Antioxidant and Antimicrobial Activities of Biomass Extracts

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4660
Author(s):  
Marta Klimek-Szczykutowicz ◽  
Michał Dziurka ◽  
Ivica Blažević ◽  
Azra Đulović ◽  
Małgorzata Miazga-Karska ◽  
...  
Keyword(s):  
Photosynthetic Pigments ◽  
Human Fibroblasts ◽  
Antimicrobial Activities ◽  
Precursor Feeding ◽  
Nasturtium Officinale ◽  
Qualitative And Quantitative ◽  
Normal Human ◽  
Inhibition Zones ◽  
Ferulic Acids ◽  
Antioxidant And Antimicrobial Activities

The study demonstrated the effects of precursor feeding on the production of glucosinolates (GSLs), flavonoids, polyphenols, saccharides, and photosynthetic pigments in Nasturtium officinale microshoot cultures grown in Plantform bioreactors. It also evaluated the antioxidant and antimicrobial activities of extracts. L-phenylalanine (Phe) and L-tryptophan (Trp) as precursors were tested at 0.05, 0.1, 0.5, 1.0, and 3.0 mM. They were added at the beginning (day 0) or on day 10 of the culture. Microshoots were harvested after 20 days. Microshoots treated with 3.0 mM Phe (day 0) had the highest total GSL content (269.20 mg/100 g DW). The qualitative and quantitative profiles of the GSLs (UHPLC-DAD-MS/MS) were influenced by precursor feeding. Phe at 3.0 mM stimulated the best production of 4-methoxyglucobrassicin (149.99 mg/100 g DW) and gluconasturtiin (36.17 mg/100 g DW). Total flavonoids increased to a maximum of 1364.38 mg/100 g DW with 3.0 mM Phe (day 0), and polyphenols to a maximum of 1062.76 mg/100 g DW with 3.0 mM Trp (day 0). The precursors also increased the amounts of p-coumaric and ferulic acids, and rutoside, and generally increased the production of active photosynthetic pigments. Antioxidant potential increased the most with 0.1 mM Phe (day 0) (CUPRAC, FRAP), and with 0.5 mM Trp (day 10) (DPPH). The extracts of microshoots treated with 3.0 mM Phe (day 0) showed the most promising bacteriostatic activity against microaerobic Gram-positive acne strains (MIC 250–500 µg/mL, 20–21 mm inhibition zones). No extract was cytotoxic to normal human fibroblasts over the tested concentration range (up to 250 μg/mL).

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