scholarly journals Toward G-Quadruplex-Based Anticancer Agents: Biophysical and Biological Studies of Novel AS1411 Derivatives

2020 ◽  
Vol 21 (20) ◽  
pp. 7781
Author(s):  
Anna M. Ogloblina ◽  
Nunzia Iaccarino ◽  
Domenica Capasso ◽  
Sonia Di Gaetano ◽  
Emanuele U. Garzarella ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Topoisomerase I ◽  
Biological Effects ◽  
Structural Features ◽  
Breast Adenocarcinoma ◽  
Sequence Length ◽  
Biological Studies ◽  
G Quadruplex ◽  
Mcf 7

Certain G-quadruplex forming guanine-rich oligonucleotides (GROs), including AS1411, are endowed with cancer-selective antiproliferative activity. They are known to bind to nucleolin protein, resulting in the inhibition of nucleolin-mediated phenomena. However, multiple nucleolin-independent biological effects of GROs have also been reported, allowing them to be considered promising candidates for multi-targeted cancer therapy. Herein, with the aim of optimizing AS1411 structural features to find GROs with improved anticancer properties, we have studied a small library of AS1411 derivatives differing in the sequence length and base composition. The AS1411 derivatives were characterized by using circular dichroism and nuclear magnetic resonance spectroscopies and then investigated for their enzymatic resistance in serum and nuclear extract, as well as for their ability to bind nucleolin, inhibit topoisomerase I, and affect the viability of MCF-7 human breast adenocarcinoma cells. All derivatives showed higher thermal stability and inhibitory effect against topoisomerase I than AS1411. In addition, most of them showed an improved antiproliferative activity on MCF-7 cells compared to AS1411 despite a weaker binding to nucleolin. Our results support the hypothesis that the antiproliferative properties of GROs are due to multi-targeted effects.

scholarly journals Tuning the Polymorphism of the Anti-VEGF G-rich V7t1 Aptamer by Covalent Dimeric Constructs

2020 ◽  
Vol 21 (6) ◽  
pp. 1963 ◽  
Author(s):  
Claudia Riccardi ◽  
Domenica Musumeci ◽  
Chiara Platella ◽  
Rosa Gaglione ◽  
Angela Arciello ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Breast Adenocarcinoma ◽  
Vascular Endothelial ◽  
Binding Ability ◽  
Biophysical Characterization ◽  
G Quadruplex ◽  
Biophysical Techniques ◽  
Endothelial Growth Factor ◽  
Thermal Stability Of ◽  
Mcf 7

In the optimization process of nucleic acid aptamers, increased affinity and/or activity are generally searched by exploring structural analogues of the lead compound. In many cases, promising results have been obtained by dimerization of the starting aptamer. Here we studied a focused set of covalent dimers of the G-quadruplex (G4) forming anti-Vascular Endothelial Growth Factor (VEGF) V7t1 aptamer with the aim of identifying derivatives with improved properties. In the design of these covalent dimers, connecting linkers of different chemical nature, maintaining the same polarity along the strand or inverting it, have been introduced. These dimeric aptamers have been investigated using several biophysical techniques to disclose the conformational behavior, molecularity and thermal stability of the structures formed in different buffers. This in-depth biophysical characterization revealed the formation of stable G4 structures, however in some cases accompanied by alternative tridimensional arrangements. When tested for their VEGF165 binding and antiproliferative activity in comparison with V7t1, these covalent dimers showed slightly lower binding ability to the target protein but similar if not slightly higher antiproliferative activity on human breast adenocarcinoma MCF-7 cells. These results provide useful information for the design of improved dimeric aptamers based on further optimization of the linker joining the two consecutive V7t1 sequences.

scholarly journals An Insight into the Mechanism of Holamine- and Funtumine-Induced Cell Death in Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5716
Author(s):  
Jelili A. Badmus ◽  
Okobi E. Ekpo ◽  
Jyoti R. Sharma ◽  
Nicole Remaliah S. Sibuyi ◽  
Mervin Meyer ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Agents ◽  
Topoisomerase I ◽  
Caspase 3 ◽  
Steroidal Alkaloids ◽  
Antiproliferative Effects ◽  
Cycle Arrest ◽  
Anticancer Effects ◽  
Apoptotic Effect ◽  
Mcf 7

Holamine and funtumine, steroidal alkaloids with strong and diverse pharmacological activities are commonly found in the Apocynaceae family of Holarrhena. The selective anti-proliferative and cell cycle arrest effects of holamine and funtumine on cancer cells have been previously reported. The present study evaluated the anti-proliferative mechanism of action of these two steroidal alkaloids on cancer cell lines (HT-29, MCF-7 and HeLa) by exploring the mitochondrial depolarization effects, reactive oxygen species (ROS) induction, apoptosis, F-actin perturbation, and inhibition of topoisomerase-I. The apoptosis-inducing effects of the compounds were studied by flow cytometry using the APOPercentageTM dye and Caspase-3/7 Glo assay kit. The two compounds showed a significantly greater cytotoxicity in cancer cells compared to non-cancer (normal) fibroblasts. The observed antiproliferative effects of the two alkaloids presumably are facilitated through the stimulation of apoptosis. The apoptotic effect was elicited through the modulation of mitochondrial function, elevated ROS production, and caspase-3/7 activation. Both compounds also induced F-actin disorganization and inhibited topoisomerase-I activity. Although holamine and funtumine appear to have translational potential for the development of novel anticancer agents, further mechanistic and molecular studies are recommended to fully understand their anticancer effects.

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.

Synthesis and Evaluation of a Series of 1,3,4-Thiadiazole Derivatives as Potential Anticancer Agents

2019 ◽  
Vol 18 (11) ◽  
pp. 1606-1616 ◽  
Author(s):  
Mehlika D. Altıntop ◽  
Belgin Sever ◽  
Ahmet Özdemir ◽  
Sinem Ilgın ◽  
Özlem Atlı ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Cell Lines ◽  
Anticancer Agents ◽  
In Vitro Assays ◽  
Breast Adenocarcinoma ◽  
Dependent Manner ◽  
Hepg2 Cell Lines ◽  
Mcf 7

Background and Methods: In an attempt to develop potent antitumor agents, the synthesis of a series of N-(6-substituted benzothiazol-2-yl)-2-[(5-(arylamino)-1,3,4-thiadiazol-2-yl)thio]acetamides (1-14) was described and their cytotoxic effects on A549 human lung adenocarcinoma, MCF-7 human breast adenocarcinoma, HepG2 human hepatocellular carcinoma and NIH/3T3 mouse embryonic fibroblast cell lines were investigated using MTT assay. <p> Results: Phenyl-substituted compounds (8-14) were found to be more effective than naphthyl-substituted compounds (1-7) on cancer cells. Compounds 8, 9, 10, 12, 13 and 14 were identified as the most potent anticancer agents on MCF-7 and HepG2 cell lines and therefore their effects on DNA synthesis and apoptosis/necrosis in MCF-7 cell line were evaluated. Among these compounds, N-(6-methoxybenzothiazol-2-yl)-2-[(5- (phenylamino)-1,3,4-thiadiazol-2-yl)thio]acetamide (13) was the most selective anticancer agent against MCF-7 and HepG2 cell lines with a SI value of 100. On the other hand, compounds 8, 9, 10, 12, 13 and 14 inhibited DNA synthesis in MCF-7 cell line in a dose-dependent manner. Flow cytometric analyses clearly indicated that the compounds showed significant anticancer activity against MCF-7 cell line via the induction of apoptosis dose dependently. <p> Conclusion: According to in vitro assays, compounds 8, 9, 10, 12, 13 and 14 stand out as promising candidates for further studies.

scholarly journals Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1374
Author(s):  
Celso Alves ◽  
Joana Silva ◽  
Susete Pinteus ◽  
Eva Alonso ◽  
Rebeca Alvariño ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Anticancer Agents ◽  
Mitochondrial Membrane ◽  
Malignant Cell ◽  
Breast Adenocarcinoma ◽  
H2o2 Production ◽  
Caspase 9 ◽  
Chemical Structures ◽  
Mcf 7

Marine natural products have exhibited uncommon chemical structures with relevant antitumor properties highlighting their potential to inspire the development of new anticancer agents. The goal of this work was to study the antitumor activities of the brominated diterpene sphaerodactylomelol, a rare example of the dactylomelane family. Cytotoxicity (10–100 µM; 24 h) was evaluated on tumor cells (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-ML-28) and the effects estimated by MTT assay. Hydrogen peroxide (H2O2) levels and apoptosis biomarkers (membrane translocation of phosphatidylserine, depolarization of mitochondrial membrane potential, Caspase-9 activity, and DNA condensation and/or fragmentation) were studied in the breast adenocarcinoma cellular model (MCF-7) and its genotoxicity on mouse fibroblasts (L929). Sphaerodactylomelol displayed an IC50 range between 33.04 and 89.41 µM without selective activity for a specific tumor tissue. The cells’ viability decrease was accompanied by an increase on H2O2 production, a depolarization of mitochondrial membrane potential and an increase of Caspase-9 activity and DNA fragmentation. However, the DNA damage studies in L929 non-malignant cell line suggested that this compound is not genotoxic for normal fibroblasts. Overall, the results suggest that the cytotoxicity of sphaerodactylomelol seems to be mediated by an increase of H2O2 levels and downstream apoptosis.

scholarly journals Synthesis and Anticancer Evaluations of Novel Thiazole Derivatives Derived from 4-Phenylthiazol-2-amine

2021 ◽  
Vol 68 (3) ◽  
pp. 604-616
Author(s):  
Amira E. M. Abdallah ◽  
Rafat M. Mohareb ◽  
Maher H. E. Helal ◽  
Germeen J. Mofeed
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
Human Cell Line ◽  
Breast Adenocarcinoma ◽  
Small Cell Lung ◽  
Thiazole Derivatives ◽  
Human Cancer Cell Lines ◽  
Chemical Reagents ◽  
Cns Cancer ◽  
Mcf 7

Many novel thiazole derivatives were designed and synthesized using 4-phenylthiazol-2-amine. The reactivity of the latter compound toward different chemical reagents was studied. The structure of the newly synthesized compounds was established based on elemental analysis and spectral data. Furthermore, twenty compounds of the synthesized systems were selected and evaluated in (μM) as significant anticancer agents towards three human cancer cell lines [MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), and SF-268 (CNS cancer)] and normal fibroblasts human cell line (WI-38). The results showed that compounds 9 and 14a displayed higher effeciency than the reference doxorubicin.

Synthesis and Biological Evaluation of New Quinoline-Based Thiazolyl Hydrazone Derivatives as Potent Antifungal and Anticancer Agents

2018 ◽  
Vol 15 (2) ◽  
pp. 193-202 ◽  
Author(s):  
Ali Erguc ◽  
Mehlika Dilek Altintop ◽  
Ozlem Atli ◽  
Belgin Sever ◽  
Gokalp Iscan ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Mtt Assay ◽  
Anticancer Agents ◽  
Mouse Embryonic Fibroblast ◽  
Biological Evaluation ◽  
Diffusion Method ◽  
Breast Adenocarcinoma ◽  
Nih 3T3 ◽  
Mcf 7

Background: In medicinal chemistry, thiazoles have gained great importance in antifungal and anticancer drug design and development. Objectives: The aim of this study was to synthesize new quinoline-based thiazolyl hydrazone derivatives and evaluate their anticandidal and anticancer effects. Methods: New thiazolyl hydrazone derivatives were evaluated for their anticandidal effects using disc diffusion method. Ames MPF assay was carried out to determine the genotoxicity of the most effective antifungal derivative. MTT assay was also performed to assess the cytotoxic effects of the compounds on A549 human lung adenocarcinoma, HepG2 human hepatocellular carcinoma, MCF- 7 human breast adenocarcinoma and NIH/3T3 mouse embryonic fibroblast (healthy) cell lines. Methods: Results: 4-(4-Fluorophenyl)-2-(2-((quinolin-4-yl)methylene)hydrazinyl)thiazole (4) showed antifungal activity against Candida albicans and Candida krusei in the concentration of 1 mg/mL. In MTT and Ames MPF tests, it was determined that compound 4 did not show cytotoxic and genotoxic effects. MTT assay indicated that 4-(naphthalen-2-yl)-2-(2-((quinolin-4-yl)methylene) hydrazinyl)thiazole (10) showed more selective anticancer activity than cisplatin against A549 and MCF-7 cell lines. Besides, 4-(4-chlorophenyl)-2-(2-((quinolin-4-yl)methylene)hydrazinyl)thiazole (5) exhibited more selective anticancer activity than cisplatin against HepG2 cell line. Conclusion: Due to their high selectivity index, these compounds are considered as candidate compounds to participate in further research.

Correlation between Antioxidant/Antimutagenic and Antiproliferative Activity of Some Phytochemicals

2019 ◽  
Vol 19 (12) ◽  
pp. 1481-1490 ◽  
Author(s):  
Doaa T. Ramadan ◽  
Mohamed A.M. Ali ◽  
Shaymaa M. Yahya ◽  
Wael M. El-Sayed
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Ellagic Acid ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Liver Cells ◽  
Antimutagenic Activity ◽  
Apoptotic Pathway ◽  
Mcf 7

Background: Chemotherapeutic drugs have high toxicity associated with undesirable side-effects. Now, natural products are the most important anti-cancer agents because of their low toxicity and potential effectiveness. Methods: The half maximal inhibitory concentration (IC50) of amygdalin, naringenin and ellagic acid against breast, colon, and liver cell lines was estimated. The antimutagenic, free radical-, superoxide radical-, and hydroxyl radical- scavenging activities of these phytochemicals were measured. The expression of p53, bid, bax, bcl2, and caspases 9, 3, and 7 was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in breast and liver cells. In addition, the active Caspase 3 protein was estimated in liver cells. Results: Ellagic acid showed the highest antioxidant and antiproliferative activities. Amygdalin and naringenin with low and moderate antioxidant profiles showed a corresponding low and moderate cytotoxicity against cancer cell lines, respectively. Naringenin and ellagic acid had a significant antimutagenic activity which was detected by the Salmonella test. Ellagic acid offered a much better antimutagenic activity than naringenin. The apoptotic pathway evoked by ellagic acid in HepG2 and MCF-7 cells was investigated. The results showed that a caspase-dependent and a caspase-independent apoptosis occurred in MCF-7 and HepG2, respectively. Conclusion: The antimutagenic/antioxidant properties are well correlated with the antiproliferative activity of the phytochemicals investigated. This study proved that some easy, quick and cheap assays could predict the antiproliferative activity of many nutraceuticals. Finally, this platform could help in the discovery of new anticancer agents where hundreds of compounds are investigated in the pipeline of drug discovery.

scholarly journals Design and Synthesis of Benzimidazole-Chalcone Derivatives as Potential Anticancer Agents

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3259 ◽  
Author(s):  
Hsieh ◽  
Ko ◽  
Chang ◽  
Kapoor ◽  
Liang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Alkyl Chain ◽  
Biological Activities ◽  
Breast Adenocarcinoma ◽  
Benzimidazole Derivatives ◽  
Design And Synthesis ◽  
Anticancer Properties ◽  
Human Ovarian Carcinoma ◽  
Mcf 7

Numerous reports have shown that conjugated benzimidazole derivatives possess various kinds of biological activities, including anticancer properties. In this report, we designed and synthesized 24 new molecules comprising a benzimidazole ring, arene, and alkyl chain-bearing cyclic moieties. The results showed that the N-substituted benzimidazole derivatives bearing an alkyl chain and a nitrogen-containing 5- or 6-membered ring enhanced the cytotoxic effects on human breast adenocarcinoma (MCF-7) and human ovarian carcinoma (OVCAR-3) cell lines. Among the 24 synthesized compounds, (2E)-1-(1-(3-morpholinopropyl)-1H-benzimidazol-2 -yl)-3-phenyl-2-propen-1-one) (23a) reduced the proliferation of MCF-7 and OVCAR-3 cell lines demonstrating superior outcomes to those of cisplatin.

scholarly journals IN VITRO CYTOTOXIC AND APOPTOTIC ACTIVITIES OF SULFATED POLYSACCHARIDE FROM CODIUM EDULE P.C. SILVA AGAINST BREAST CANCER ADENOCARCINOMA

2019 ◽  
pp. 17-21
Author(s):  
ARIANE MARIE G BAYRO ◽  
MARY JHO-ANNE T CORPUZ ◽  
ROSS D VASQUEZ
Keyword(s):  
Antiproliferative Activity ◽  
Caspase 3 ◽  
Annexin V ◽  
Sulfated Polysaccharide ◽  
Hot Water ◽  
Breast Adenocarcinoma ◽  
Significant Difference ◽  
Ft Ir ◽  
Mcf 7

Objective: The primary purpose of this study is to characterize Codium edule crude sulfated polysaccharide (CSP) and its fractions and to determineits potential antiproliferative and apoptotic properties.Methods: The CSP was obtained through hot water extraction followed by precipitation with absolute ethanol. CSP was further purified using ionexchangechromatography, Sepharose DEAE Fast Flow column and yielded three fractions (F1, F2, and F3). The CSP and fractions were characterizedfor their sulfate, protein, carbohydrate, and uronic acid content. Fourier-transformed infrared spectroscopy (FT-IR) was used to determine thefunctional groups present in CSP and SP fractions. Antiproliferative activity against human breast adenocarcinoma (MCF-7) was analyzed using MTTassay with doxorubicin as positive control. Apoptotic activity of C. edule was analyzed using caspase 3/7 and annexin V-FITC assay.Results: CSP afforded 6.3% sulfate, 4.1% protein, and 68.7% carbohydrate. F1 has the highest content of sulfate, protein, carbohydrate, and uronicacid among the fractions. FT-IR shows a broadband around 3400 cm−1 indicates the presence of hydroxyl stretching vibration of polysaccharide (-OH)and a band at 2922 cm−1 suggests a C-H stretch (alkane). 1658 cm−1 may be attributed to the C=O stretches of amide C=N group. Peak around 1259 cm−1is a characteristic band for S=O sulfate ester. The antiproliferative activity of C. edule against MCF-7 showed significant difference in the mean percentinhibition between CSP and F3 (p=0.001), F1 and F3 (p≤0.001), F2 and doxorubicin (p=0.025), and F3 and doxorubicin (p≤0.000). F1 of C. edule hasthe lowest IC50 of 5.54 μg/ml and displayed apoptotic phase and caspase 3/7 activity.Conclusion: The investigation revealed that SP from green seaweed, C. edule, could be used as potential anticancer treatment against breast canceradenocarcinoma.

Sign in / Sign up

Export Citation Format

Share Document