Ru(III) complexes of pyrazolopyrimidines as anticancer agents: In vitro, in vivo anticancer activity and underlying multi-mechanisms

2022 ◽  
Author(s):  
Yunqiong Gu ◽  
Wen-Ying Shen ◽  
Qi-Yuan Yang ◽  
Zhen-Feng Chen ◽  
Hong Liang
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Human Liver ◽  
Normal Human Liver ◽  
Normal Human ◽  
Low Toxicity

Three ruthenium(III) complexes with pyrazolopyrimidine [Ru(Ln)(H2O)Cl3] (13, n=13) were prepared and characterized. These Ru(III) compounds show strong cytotoxicity against six cancer cell lines and low toxicity to normal human liver...

scholarly journals Anticancer Activity of Cynomorium coccineum

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 354 ◽  
Author(s):  
Mouna Sdiri ◽  
Xiangmin Li ◽  
William Du ◽  
Safia El-Bok ◽  
Yi-Zhen Xie ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Cycle Progression

The extensive applications of Cynomorium species and their rich bioactive secondary metabolites have inspired many pharmacological investigations. Previous research has been conducted to examine the biological activities and numerous interesting pharmaceutical activities have been reported. However, the antitumor activities of these species are unclear. To understand the potential anticancer activity, we screened Cynomorium coccineum and Cynomorium songaricum using three different extracts of each species. In this study, the selected extracts were evaluated for their ability to decrease survival rates of five different cancer cell lines. We compared the cytotoxicity of the three different extracts to the anticancer drug vinblastine and one of the most well-known medicinal mushrooms Amaurederma rude. We found that the water and alcohol extracts of C. coccineum at the very low concentrations possessed very high capacity in decreasing the cancer cells viability with a potential inhibition of tumorigenesis. Based on these primitive data, we subsequently tested the ethanol and the water extracts of C. coccineum, respectively in in vitro and in vivo assays. Cell cycle progression and induction of programmed cell death were investigated at both biological and molecular levels to understand the mechanism of the antitumor inhibitory action of the C. coccineum. The in vitro experiments showed that the treated cancer cells formed fewer and smaller colonies than the untreated cells. Cell cycle progression was inhibited, and the ethanol extract of C. coccineum at a low concentration induced accumulation of cells in the G1 phase. We also found that the C. coccineum’s extracts suppressed viability of two murine cancer cell lines. In the in vivo experiments, we injected mice with murine cancer cell line B16, followed by peritoneal injection of the water extract. The treatment prolonged mouse survival significantly. The tumors grew at a slower rate than the control. Down-regulation of c-myc expression appeared to be associated with these effects. Further investigation showed that treatment with C. coccineum induced the overexpression of the tumor suppressor Foxo3 and other molecules involved in inducing autophagy. These results showed that the C. coccineum extract exerts its antiproliferative activity through the induction of cell death pathway. Thus, the Cynomorium plants appear to be a promising source of new antineoplastic compounds.

scholarly journals Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo

2019 ◽  
Vol 39 (11) ◽  
pp. 5973-5982 ◽  
Author(s):  
SACHIKO OGASAWARA ◽  
YUTARO MIHARA ◽  
REIICHIRO KONDO ◽  
HIRONORI KUSANO ◽  
JUN AKIBA ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Liver ◽  
Antiproliferative Effect ◽  
Liver Cancer Cell ◽  
Human Liver Cancer Cell ◽  
Human Liver Cancer

scholarly journals Potent In Vitro and In Vivo Anticancer Activity of New Bipyridine and Bipyrimidine Gold (III) Dithiocarbamate Derivatives

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 474 ◽  
Author(s):  
Muhammad Altaf ◽  
Naike Casagrande ◽  
Elena Mariotto ◽  
Nadeem Baig ◽  
Abdel-Nasser Kawde ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Ros Generation ◽  
Dna Breaks

We synthesized eight new bipyridine and bipyrimidine gold (III) dithiocarbamate-containing complexes (C1–C8) and tested them in a panel of human cancer cell lines. We used osteosarcoma (MG-63), lung (A549), prostate (PC3 and DU145), breast (MCF-7), ovarian (A2780 and A2780cis, cisplatin- and doxorubicin-resistant), and cervical (ME-180 and R-ME-180, cisplatin resistant) cancer cell lines. We found that C2, C3, C6, and C7 were more cytotoxic than cisplatin in all cell lines tested and overcame cisplatin and doxorubicin resistance in A2780cis and R-ME-180 cells. In the PC3 prostate cancer cell line, the gold (III) complex C6 ([Au2(BPM)(DMDTC)2]Cl4) induced apoptosis and double-stranded DNA breaks, modified cell cycle phases, increased Reactive Oxigen Species (ROS) generation, and reduced thioredoxin reductase and proteasome activities. It inhibited PC3 cell migration and was more cytotoxic against PC3 cells than normal human adipose-derived stromal cells. In mice bearing PC3 tumor xenografts, C6 reduced tumor growth by more than 70% without causing weight loss. Altogether, our results demonstrate the anticancer activity of these new gold (III) complexes and support the potential of C6 as a new agent for prostate cancer treatment.

Synthesis and In Vitro Anticancer Activity of 6-Ferrocenylpyrimidin-4(3H)-one Derivatives

2019 ◽  
Vol 16 (1) ◽  
pp. 160-164 ◽  
Author(s):  
Stanislav A. Grabovskiy ◽  
Rinat S. Muhammadiev ◽  
Lenar R. Valiullin ◽  
Ivan S. Raginov ◽  
Natalie N. Kabal'nova
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Practical Interest ◽  
Breast Adenocarcinoma ◽  
Human Skin Fibroblast ◽  
Normal Human Skin ◽  
Normal Human ◽  
Mcf 7

Aim and Objective: Some ferrocenyl derivatives are active in vitro and in vivo against cancer. Generally, ferrocenyl derivatives for cancer research have three key components: a ferrocene moiety, a conjugated linker that lowers the oxidation potential and some derivative (peptide, nucleobase and others) that can interact with biomolecules. Since the pyrimidine fragment can easily pass through the membrane into the cells and become involved in metabolism; it appears to be promising. Furthermore, this fragment is an electron-acceptor group, so a spacer can be excluded. Therefore, the synthesis of 6-ferrocenylpyrimidin-4(3H)-one derivatives and the study of their anticancer activity have scientific and practical interest. </P><P> Methods: The syntheses of 6-ferrocenylpyrimidin-4(3H)-one derivatives were performed by the condensation of ethyl 3-ferrocenyl-3-oxopropionate with thiourea or acetamidine or guanidine. The cytotoxicity of four 6- ferrocenylpyrimidin-4(3H)-one derivatives was evaluated by using the MTT assay in vitro against Human breast adenocarcinoma MCF-7 and normal human skin fibroblast HSF cells. The tested derivatives induced a concentration-dependent cytotoxic response in cell lines. </P><P> Results: A study of the cytotoxic activity of 6-ferrocenylpyrimidin-4(3H)-one derivatives by the MTT test has found that all compounds have a dose-dependent toxic effect on the lines of breast cancer cells (MCF-7) and normal human fibroblast cells (HSF). The most pronounced cytotoxic effect is exhibited by 2-methyl-6-ferrocenylpyrimidin- 4(3H)-one (MCF-7, IC50 17 ± 1 µM). Conclusion: The experimental results confirm the importance of investigation and design of ferrocenylpyrimidin- 4(3H)-one derivatives as anticancer agents. Compounds where the pyrimidine derivatives are directly linked to the ferrocene unit rather than via a spacer group also may be of interest for antiproliferative drug design.

scholarly journals Anticancer activity of oncolytic adenoviruses carrying p53 is augmented by 11R in gallbladder cancer cell lines in vitro and in vivo

2013 ◽  
Vol 30 (2) ◽  
pp. 833-841 ◽  
Author(s):  
JINGHAN WANG ◽  
YONG YU ◽  
ZI YAN ◽  
ZHENLI HU ◽  
LINFANG LI ◽  
...  
Keyword(s):  
Gallbladder Cancer ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Oncolytic Adenoviruses

scholarly journals Design, Synthesis, and Biological Evaluation of Novel N-Acylhydrazone Bond Linked Heterobivalent β-Carbolines as Potential Anticancer Agents

Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2950 ◽  
Author(s):  
Chen ◽  
Guo ◽  
Ma ◽  
Chen ◽  
Fan ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Chorioallantoic Membrane ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
In Vivo Model ◽  
Ic50 Values

Utilizing a pharmacophore hybridization approach, we have designed and synthesized a novel series of 28 new heterobivalent β-carbolines. The in vitro cytotoxic potential of each compound was evaluated against the five cancer cell lines (LLC, BGC-823, CT-26, Bel-7402, and MCF-7) of different origin—murine and human, with the aim of determining the potency and selectivity of the compounds. Compound 8z showed antitumor activities with half-maximal inhibitory concentration (IC50) values of 9.9 ± 0.9, 8.6 ± 1.4, 6.2 ± 2.5, 9.9 ± 0.5, and 5.7 ± 1.2 µM against the tested five cancer cell lines. Moreover, the effect of compound 8z on the angiogenesis process was investigated using a chicken chorioallantoic membrane (CAM) in vivo model. At a concentration of 5 μM, compound 8z showed a positive effect on angiogenesis. The results of this study contribute to the further elucidation of the biological regulatory role of heterobivalent β-carbolines and provide helpful information on the development of vascular targeting antitumor drugs.

Synthesis, cytotoxicity and in silico study of some novel benzocoumarin-chalcone-bearing aryl ester derivatives and benzocoumarin-derived arylamide analogs

2021 ◽  
Vol 76 (3-4) ◽  
pp. 201-210
Author(s):  
Nabeel A. Abdul-Ridha ◽  
Afraah D. Salmaan ◽  
Rita Sabah ◽  
Bahjat Saeed ◽  
Najim A. Al-Masoudi
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Human Liver ◽  
Hydrophobic Interactions ◽  
Cytotoxic Agents ◽  
Cytotoxic Activities ◽  
Protein Receptor ◽  
Normal Human Liver ◽  
Normal Human

Abstract The development of new prostate cancer protein receptor cytochrome P450 17A1 inhibitors offers the possibility of generating structures of increased potency. To this end, the chalcone analogs 7 and 8 were prepared from treatment of methyl 3-oxo-3H-benzocoumarin-2-carboxylate (4) with aryl aldehydes. Treatment of 7 and 8 with three anti-inflammatory drugs, flurbiprofen, ketoprofen and ibuprofen, in the presence of POCl3/DMAP gave the ester analogs 9–12. Analogously, treatment of ethyl 3-oxo-3H-benzocoumarin-2-carboxylate (15), prepared previously from 2-hydroxy-1-naphthaldehyde (13) and dimethylmalonate (14), with various arylamines: 4-bromoaniline, 2-amino-6-methylpyridine, amino-antipyrine and 2-amino-5-nitrothiazole, in the presence of potassium tert-butoxide gave the benzocoumarine-3-arylamide analogs. The in vitro cytotoxic activities of 9–12 and 16–19 were evaluated against human prostate cancer cell lines (PC-3) and normal human liver epithelia (WRL-68) by MTT assay. Compounds 10 and 17 were the most active cytotoxic agents among the series against PC-3 cells with IC50 values of 71.35 and 78.25 μg mL–1 with SI values of 3.0 and 4.2, respectively (calculated from the cytotoxicity effects of 10 and 17 on the normal human liver epithelia [WRL-68]). Furthermore, compounds 11 and 12 were tested against breast cancer (HER2 cell lines), prostate cancer (DU-135 cell lines) and MCF-7 but were inactive. Molecular docking studies between the protein receptor CYPP450 17A1 and compounds 10 and 17 revealed that these compounds primarily form hydrophobic interactions with the receptor.

Effect of l-alanine infusion on 31P nuclear magnetic resonance spectra of normal human liver: towards biochemical pathology in vivo

1992 ◽  
Vol 83 (2) ◽  
pp. 183-190 ◽  
Author(s):  
P. C. Dagnelie ◽  
D. K. Menon ◽  
I. J. Cox ◽  
J. D. Bell ◽  
J. Sargentoni ◽  
...  
Keyword(s):  
Body Weight ◽  
Human Liver ◽  
Pulse Sequence ◽  
Whole Body ◽  
Maximal Increase ◽  
Normal Human Liver ◽  
Normal Human ◽  
Biochemical Pathology

1. 31P n.m.r. spectroscopy in vivo was used to study the effect of l-alanine infusion on the concentrations of gluconeogenic intermediates in normal human liver. Studies were performed in six healthy male subjects (34–44 years, fasted overnight) using a chemical shift imaging pulse sequence on a whole-body n.m.r. system operating at 1.6T. Hepatic 31P n.m.r. spectra were obtained from 10 min before to 70 min after intravenous administration of 0.70 (n = 2), 1.40 (n = 3) or 2.80 (n = 5) nmol of l-alanine/kg body weight over 4.5 min. Concentrations of phosphomonoesters, Pi and phosphodiesters relative to ATP were calculated from peak areas in the n.m.r. spectra, using the β-ATP peak as a reference. 2. Dose-dependent spectral changes were observed for [phosphomonoesters]/[ATP] and [Pi]/[ATP]. At the highest dose given, maximal changes in [phosphomonoesters]/[ATP] (mean ± sem: 98 ± 12%, P<0.005) and [Pi]/[ATP] (−33 ± 3%, P<0.001) were observed approximately 45 min after the l-alanine infusion. [Phosphodiesters]/[ATP] showed a maximal increase of 24 ± 6% (P<0.05), which was independent of the l-alanine dose. Hepatic ATP levels and pH did not change. 3. To identify the metabolites responsible for the changes observed in vivo, male Wistar rats were infused with 11.2 mmol of l-alanine/kg body weight. After 15 min, livers were freeze-clamped and were extracted according to standard procedures. In vitro, 31P n.m.r. spectra obtained at 8.4 or 11.7 T revealed sharp increases in the concentrations of 3-phosphoglycerate and phosphoenolpyruvate after l-alanine infusion. No significant increases in other metabolites contributing to the phosphomonoester or phosphodiester resonances in vivo were observed, suggesting that the rise in [phosphomonoesters] observed in vivo was caused by increasing concentrations of 3-phosphoglycerate, and that phosphoenolpyruvate contributed to the rise in [phosphodiesters]. 5. These results show that l-alanine infusion leads to consistent changes in the 31P n.m.r. spectra of the human liver owing to increased concentrations of gluconeogenic intermediates. The ‘n.m.r.-alanine test’ may constitute a useful tool for studies of gluconeogenesis and hepatic biochemical pathology in vivo.

scholarly journals EVALUATION OF IN VITRO CYTOTOXIC AND ANTICANCER ACTIVITY OF HEPATOPROTECTIVE POLYHERBAL FORMULATION IN CELL LINE MODEL

2019 ◽  
pp. 320-325
Author(s):  
JAYACHANDRA KUNCHA ◽  
THIRUGNANASAMBANTHAM P ◽  
KUMARAN S ◽  
NARAYANAN N ◽  
SHARMILA DEVI V
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Kidney Cell ◽  
Normal Liver ◽  
Cancer Cell Lines ◽  
Polyherbal Formulation ◽  
Ic50 Values

Introduction: The use of natural products as anticancer agents has a long history that began with folklore medicine and through the years has been incorporated into traditional and allopathic medicine. Several drugs currently used are derived from medicinal plants. Objective: The main objective of this study is to investigate the cytotoxic potential of hepatoprotective polyherbal formulation in normal and cancer cell lines. Methods: A 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was utilized to screen the cytotoxic activity. Results: The results revealed that the formulation does not induce much mortality in normal liver and kidney cell lines, and LC50 value of liver cell lines was found 1716.355 μg/ml and kidney cell lines 2464.910 μg/ml. The in vitro anticancer activity was performed on liver, colon, and prostate cancer cell lines, and IC50 values are found 2.077, 3.850, and 11.989 μg/ml, respectively, which show excellent anticancer activity. Conclusion: Based on the results obtained, the hepatoprotective polyherbal formulation is safe for normal cells and cytotoxic for cancer cells. Further, identification and quantification of phytoconstituents responsible for the activity are in progress.

scholarly journals In vitro Anticancer Activity of Marine Sponges Against T47D and HeLa Cell Lines

2020 ◽  
Vol 19 (1) ◽  
pp. 25-28
Author(s):  
Suciati ◽  
Lusiana Arifianti
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Line ◽  
Marine Sponges ◽  
Hela Cell Lines

Marine sponges have been known as the source of natural products. Various metabolites with potent bioactivities have been reported from this organism. The current study aims to investigate the anticancer potency of three marine sponges namely Diacarnus debeauforti, Haliclona amboinensis and Agelas cavernosa collected from Barrang Lompo Island, South Sulawesi, Indonesia. The ethyl acetate extracts of the sponges were screened against T47D breast cancer cells and HeLa cervical cancer cells by using the MTT method. The results showed that these sponges demonstrated anticancer activity against both cancer cell lines. The lowest IC50 of 18.2 μg/ml was given by the extract of A. cavernosa against T47D cell line, while in the screening against HeLa cancer cell line, the extract of D. debeauforti revealed the highest potency with IC50 of 15.7 μg/ml. Our results suggested that the marine sponges namely D. debeauforti, H. amboinensis and A. cavernosa can be good candidates for the development of anticancer agents. Dhaka Univ. J. Pharm. Sci. 19(1): 25-28, 2020 (June)

Sign in / Sign up

Export Citation Format

Share Document