Tunable Cytotoxicity and Selectivity of Phosphonium Ionic Liquid with Aniline Blue Dye

2021 ◽  
Vol 21 (12) ◽  
pp. 6143-6150
Author(s):  
Samantha Macchi ◽  
Mohd Zubair ◽  
Nawab Ali ◽  
Grégory Guisbiers ◽  
Noureen Siraj
Keyword(s):  
Ionic Liquid ◽  
Cell Line ◽  
Chemotherapeutic Agents ◽  
Single Step ◽  
Aniline Blue ◽  
Epithelial Cell Line ◽  
Blue Dye ◽  
Spectroscopic Techniques ◽  
Mcf 7

Ionic liquids are an interesting class of materials that have recently been utilized as chemotherapeutic agents in cancer therapy. Aniline blue, a commonly used biological staining agent, was used as a counter ion to trihexyltetradecylphosphonium, a known cytotoxic cation. A facile, single step ion exchange reaction was performed to synthesize a fluorescent ionic liquid, trihexyltetradecylphosphonium aniline blue. Aqueous nanoparticles of this hydrophobic ionic liquid were prepared using reprecipitationmethod. The newly synthesized ionic liquid and subsequent nanoparticles were characterized using various spectroscopic techniques. Transmission electron microscopy and zeta potential measurements were performed to characterize the nanoparticles’ morphology and surface charge. The photophysical properties of the nanoparticles and the parent aniline blue compound were studied using absorption and fluorescence spectroscopy. Cell viability studies were conducted to investigate the cytotoxicity of the newly developed trihexyltetradecylphosphonium aniline blue nanoparticles in human breast epithelial cancer cell line (MCF-7) and its corresponding normal epithelial cell line (MCF-10A) in vitro. The results revealed that the synthesized ionic nanomedicines were more cytotoxic (lower IC50) than the parent chemotherapeutic compound in MCF-7 cells. Nanoparticles of the synthesized ionic liquid were also shown to be more stable in both aqueous and cellular media and more selective than parent compounds towards cancer cells.

scholarly journals A Combination of an Antimitotic and a Bromodomain 4 Inhibitor Synergistically Inhibits the Metastatic MDA-MB-231 Breast Cancer Cell Line

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Thandi Mqoco ◽  
André Stander ◽  
Anna-Mart Engelbrecht ◽  
Anna M Joubert
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Current chemotherapeutic agents have many side effects and are toxic to normal cells, providing impetus to identify agents that can effectively eliminate tumorigenic cells without damaging healthy cells. The aim of this study was to examine whether combining a novel BRD4 inhibitor, ITH-47, with the antimitotic estradiol analogue, ESE-15-ol, would have a synergistic effect on inhibiting the growth of two different breast cancer cell lines in vitro. Our docking and molecular dynamics studies showed that compared to JQ1, ITH-47 showed a similar binding mode with hydrogen bonds forming between the ligand nitrogens of the pyrazole, ASN99, and water of the BRD4 protein. Data from cell growth studies revealed that the GI50 of ITH-47 and ESE-15-ol after 48 hours of exposure was determined to be 15 μM and 70 nM, respectively, in metastatic MDA-MB-231 breast cancer cells. In tumorigenic MCF-7 breast cancer cells, the GI50 of ITH-47 and ESE-15-ol was 75 μM and 60 nM, respectively, after 48 hours of exposure. Furthermore, the combination of 7.5 μM and 14 nM of ITH-47 and ESE-15-ol, respectively, resulted in 50% growth inhibition of MDA-MB-231 cells resulting in a synergistic combination index (CI) of 0.7. Flow cytometry studies revealed that, compared to the control, combination-treated MDA-MB-231 cells had significantly more cells present in the sub-G1 phase and the combination treatment induced apoptosis in the MDA-MB-231 cells. Compared to vehicle-treated cells, the combination-treated cells showed decreased levels of the BRD4, as well as c-Myc protein after 48 hours of exposure. In combination, the selective BRD4 inhibitor, ITH-47, and ESE-15-ol synergistically inhibited the growth of MDA-MB-231 breast cancer cells, but not of the MCF-7 cell line. This study provides evidence that resistance to BRD4 inhibitors may be overcome by combining inhibitors with other compounds, which may have treatment potential for hormone-independent breast cancers.

scholarly journals Design and synthesis of highly oxygenated furo[3,2-c]pyran-4-ones and furo[3,2-c]chromen-4-ones scaffold as potential anticancer and antimicrobial agent

2021 ◽  
Author(s):  
Suman Rani ◽  
Nisha Kamra ◽  
Sumit Thakral ◽  
Devinder Kumar ◽  
Ajeet Singh ◽  
...  
Keyword(s):  
Cell Line ◽  
Cancer Cell Line ◽  
Spectroscopic Techniques ◽  
One Pot ◽  
Design And Synthesis ◽  
Dehydroacetic Acid ◽  
Different Strains ◽  
Antibacterial And Antifungal ◽  
Mcf 7

Synthesis of a number of highly oxygenated furo[3,2-c]pyran-4-one (4, 5) and furo[3,2-c]chromen-4-one (8, 9) has been accomplished by a simple one pot reaction from easily available versatile starting materials - dehydroacetic acid and 3-acetyl-4-hydroxycoumarin. All the synthesized molecules were characterized utilizing various spectroscopic techniques and screened for anticancer activity (in vitro) against three Colon (HCT-116, SW-620, HT-24), Lung (A-549), Prostate-(PC-3), Breast-(MCF-7) cell lines. Compounds 5a, 9d, 9f showed good activity against breast MCF-7 cancer cell line having IC50 values 6.9, 2.8, 5.3 µM, respectively. Out of these compound 9d showed better activity against prostate PC-3 cell line with IC50 value 3.8 µM. The synthesized compounds were also studied for potential antibacterial activity (in vitro) using different strains of bacteria (Bacillus subtilis and Staphylococcus aureus -Gram-positive, and Escherichia coli- Gram negative) as well as fungal strains (Aspergillus niger and Candida albicans) using Norfloxacin and Fluconazole as antibacterial and antifungal standard drugs, respectively. The outcome of the antimicrobial screening study showed that compound 9f exhibited promising activity against S. aureus and B. subtilis while 5h showed excellent and 5i and 9b showed better activity against E. coli. The compounds 5c-5e displayed excellent activity against C. albicans and A. niger than Fluconazole.

scholarly journals Am Synthesis, Docking Study and In vitro Anticancer Evaluation of Some New Flurbiprofen Derivatives Against MCF-7 and WRL-68 Cell Lines

2021 ◽  
Author(s):  
Kasim S. Hmood ◽  
Ammar A. Razzak Mahmood Kubba ◽  
Redha I Al-bayati ◽  
Abdulrahman M. Saleh
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Docking Study ◽  
Spectroscopic Techniques ◽  
Cytotoxic Assay ◽  
Molecular Docking Study ◽  
Thiourea Derivatives ◽  
Starting Point ◽  
Mcf 7

A new series of flurbiprofen derivatives containing thiosemicarbazide moiety (3-7)  was  synthesized from flurbiprofen as parent nucleus by  esterification, hydrazide formation, and  heating with different  aryl isothiocyanate substituents, respectively. Flurbiprofen was also treated with thiosemicarbazide in the  presence POCl3 as  a catalyst,   to produce 1,3,4 -thiadiazole -2-amine (8). Treatment of (8) with different aryl isothiocyanates  produced thiourea derivatives (9-12).  Also, the reaction of  (8)  with different benzoyl chloride substituents produced benzamide compounds (13-15). Eventually , treatment of (8)  with  ethyl acetoacetate(EAA) produced [1,3,4]thiadiazolo[3,2-a]pyrimidin-7-one (16) .The new compounds were  characterized by spectroscopic techniques :FTIR,  1HNMR, and CHNS analysis. A molecular docking  study for  the  synthesized compounds (3-16), against the Vascular Endothelial Growth Factor receptor (VEGFR-2) was applied   and  it  indicated  that compounds 4,7,13, and 15,exhibited the optimum binding energy of     -6.77, -6.12,-6.68, and -6.43 kcal/mol, respectively. Target compounds were  also assessed  for their  in vitro anticancer effects  in a cell-line study. All  of the compounds tested  showed  the most plausible anticancer activity, compared to a positive control(Sorafenib), using in vitro  MTT cytotoxic assay ,against human breast tumor (MCF-7), and normal WRL-68 cell line. The in vitro results revealed that compounds 4,5,10,11,13, and 15 exhibited the highest inhibitory activity at their IC50 concentrations, against MCF-7 cell lines, as follows (122.7,113.9,95,7. 109.1,40.32 and 112.29µg/mL, respectively. While their cytotoxic effect against normal WRL-68 cell line at  their IC50 concentrations, as follow 210.2, 181.3 ,151.7,278.7,80.28, and 236 µg/mL, respectively, therefore,  such compounds were considered more selective toward MCF-7 than normal WRL-68,and their selectivity index (SI): 1.71,1.59,1.59 ,2.55 ,1.99 , and 2.10,respectively . Among the synthesized compounds, the compound 15 was chosen to screen its effect in vitro through multi-parameter cytotoxic assay against MCF-7 breast cancer implemented in High Content Screening (ArrayScan XTI, Thermo Scientific),which  could be taken in consideration as a starting point for the  development  of new anticancer drugs

Deciphering of The Effect of Chemotherapeutic Agents on Human Glutathione S-Transferase Enzyme and MCF-7 Cell Line

2020 ◽  
Vol 27 (9) ◽  
pp. 888-894
Author(s):  
Havva Aybek ◽  
Yusuf Temel ◽  
Barzan Mirza Ahmed ◽  
Can Ali Ağca ◽  
Mehmet Çiftci
Keyword(s):  
Cell Line ◽  
Human Erythrocyte ◽  
Chemotherapeutic Agents ◽  
Cellular Viability ◽  
Ammonium Sulfate Precipitation ◽  
Glutathione S Transferase ◽  
In Vitro Effects ◽  
First Time ◽  
Mcf 7

Background: Cancer is the disease that causes the most death after cardiovascular diseases all over the world these days. Breast cancer is the most common type of cancer among women and ranks the second among cancer-related deaths after lung cancer. Chemotherapeutics act by killing cancer cells, preventing their spread and slowing their growth. Recent studies focus on the effects of chemotherapeutics on cancer cells and new chemotherapy approaches that targeting enzymes that catalyze important metabolic reactions in the cell. Objective: The aim of this study was to investigate the effects of chemotherapeutic agents, Tamoxifen and 5-FU, on MCF-7 cell line and human erythrocyte GST, an important enzyme of intracellular antioxidant metabolism. Methods: In this study, it was investigated that the effect of chemotherapeutic agents, Tamoxifen and 5-FU, on MCF-7 breast cancer cell line and performed ROS analyzes. In addition, it was purified glutathione S-transferase (GST), one of the important enzymes of intracellular antioxidant mechanism, from human erythrocytes by using ammonium sulfate precipitation and glutathione agarose affinity chromatography, and investigated in vitro effects of chemotherapeutic agents, 5 - FU and Tamoxifen, on the activity of this enzyme for the first time. Results: it was determined that Tamoxifen and 5-FU inhibited cellular viability and 5-FU increased intracellular levels of ROS, whereas Tamoxifen reduced intracellular levels of ROS. In addition, human erythrocyte GST enzyme with 16.2 EU/mg specific activity was purified 265.97-fold with a yield of 35% using ammonium sulfate precipitation and glutathione agarose affinity chromatography. The purity of the enzyme was checked by the SDS-PAGE method. In vitro effects of chemotherapeutics, 5-FU and Tamoxifen, on GST activity purified from human erythrocytes were investigated. The results showed that 5-FU increased the activity of GST in the concentration range of 77 to 1155 μM and that Tamoxifen increased the activity of GST in the concentration range of 0.54 to 2.70 μM. Conclusion: In this study, the effects of tamoxifen and 5-FU chemotherapeutic agents on both MCF-7 cell line and human GST enzyme were examined together for the first time. Our study showed that chemotherapeutic agents (5-FU and Tamoxifen) inhibited cellular viability and Tamoxifen reduced intracellular levels of ROS whereas 5-FU increased intracellular levels of ROS. In addition, 5-FU and Tamoxifen were found to increase the activity of GST enzyme purified from the human erythrocyte.

scholarly journals Chlamydial clinical isolates show subtle differences in persistence phenotypes and growth in vitro

2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Mark Thomas ◽  
Amba Lawrence ◽  
Samuel Kroon ◽  
Lenka A. Vodstrcil ◽  
Samuel Phillips ◽  
...  
Keyword(s):  
Cell Line ◽  
Type Strain ◽  
Type Species ◽  
Clinical Isolates ◽  
Epithelial Cell Line ◽  
Content Type ◽  
Link Type ◽  
Type Strains ◽  
Mcf 7

Urogenital Chlamydia trachomatis infection is the most common sexually transmitted bacterial infection throughout the world. While progress has been made to better understand how type strains develop and respond to environmental stress in vitro, very few studies have examined how clinical isolates behave under similar conditions. Here, we examined the development and persistence phenotypes of several clinical isolates, to determine how similar they are to each other, and the type strain C. trachomatis D/UW-3/Cx. The type strain was shown to produce infectious progeny at a higher magnitude than each of the clinical isolates, in each of the six tested cell lines. All chlamydial strains produced the highest number of infectious progeny at 44 h post-infection in the McCoy B murine fibroblast cell line, yet showed higher levels of infectivity in the MCF-7 human epithelial cell line. The clinical isolates were shown to be more susceptible than the type strain to the effects of penicillin and iron deprivation persistence models in the MCF-7 cell line. While subtle differences between clinical isolates were observed throughout the experiments conducted, no significant differences were identified. This study reinforces the importance of examining clinical isolates when trying to relate in vitro data to clinical outcomes, as well as the importance of considering the adaptations many type strains have to being cultured in vitro.

scholarly journals Comparison of in Vitro Cytotoxicity and Apoptogenic Activity of Magnesium Chloride and Cisplatin as Conventional Chemotherapeutic Agents in the MCF-7 Cell Line

2016 ◽  
Vol 17 (sup3) ◽  
pp. 131-134 ◽  
Author(s):  
Seyed Abbas Mirmalek ◽  
Ehsan Jangholi ◽  
Mohammad Jafari ◽  
Soheila Yadollah-Damavandi ◽  
Mohammad Amin Javidi ◽  
...  
Keyword(s):  
Cell Line ◽  
Magnesium Chloride ◽  
Chemotherapeutic Agents ◽  
In Vitro Cytotoxicity ◽  
Mcf 7

A Novel Triazole Derivative Drug Presenting In Vitro and In Vivo Anticancer Properties

2018 ◽  
Vol 18 (17) ◽  
pp. 1483-1493
Author(s):  
Ricardo Imbroisi Filho ◽  
Daniel T.G. Gonzaga ◽  
Thainá M. Demaria ◽  
João G.B. Leandro ◽  
Dora C.S. Costa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Hepatic Function ◽  
Anticancer Properties ◽  
Mcf 7

Background: Cancer is a major cause of death worldwide, despite many different drugs available to treat the disease. This high mortality rate is largely due to the complexity of the disease, which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching for novel drugs that can target different and multiple aspects of cancer. Experimental: After a screening, we selected one novel molecule, out of ninety-four triazole derivatives, that strongly affects the viability and proliferation of the human breast cancer cell line MCF-7, with minimal effects on non-cancer cells. The drug, named DAN94, induced a dose-dependent decrease in MCF-7 cells viability, with an IC50 of 3.2 ± 0.2 µM. Additionally, DAN94 interfered with mitochondria metabolism promoting reactive oxygen species production, triggering apoptosis and arresting the cancer cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects are not observed when the drug was tested in the non-cancer cell line MCF10A. Using a mouse model with xenograft tumor implants, the drug preventing tumor growth presented no toxicity for the animal and without altering biochemical markers of hepatic function. Results and Conclusion: The novel drug DAN94 is selective for cancer cells, targeting the mitochondrial metabolism, which culminates in the cancer cell death. In the end, DAN94 has been shown to be a promising drug for controlling breast cancer with minimal undesirable effects.

Synthesis, Docking Study, Cytotoxicity, Antioxidant, and Anti-microbial Activities of Novel 2,4-Disubstituted Thiazoles Based on Phenothiazine

2020 ◽  
Vol 17 (2) ◽  
pp. 151-159
Author(s):  
Tran Nguyen Minh An ◽  
Pham Thai Phuong ◽  
Nguyen Minh Quang ◽  
Nguyen Van Son ◽  
Nguyen Van Cuong ◽  
...  
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Antimicrobial Activities ◽  
Significant Activity ◽  
Thiazole Derivatives ◽  
Ligand Interaction ◽  
Ic50 Value ◽  
Mcf 7

: A series of novel 1,3-thiazole derivatives (5a-i) with a modified phenothiazine moiety were synthesized and tested against cancer cell line MCF-7 for their cytotoxicity. Most of them (5a-i) were less cytotoxic or had no activity against MCF-7 cancer cell line. Material and Methods: The IC50 value of compound (4) was 33.84 μM. The compounds (5a-i) were also evaluated for antimicrobial activities, but no significant activity was observed. The antioxidant activity was conducted for target compounds (5a-i). The IC50 value of compound (5b) was 0.151mM. Results: The total amount of energy, ACE (atomic contact energy), energy of receptor (PDB: 5G5J), and ligand interaction of structure (4) were found to be 22.448 Kcal.mol-1 , -247.68, and -91.91 Kcal.mol-1, respectively. The structure (4) is well binded with the receptor because the values of binding energy, steric energy, and the number of hydrogen bondings are -91.91, 22.448 kcal.mol-1, and 2, respectively. It shows that structure (4) has good cytotoxicity with MCF-7 in vitro. Conclusion: The increasing of docking ability of structures (5a-i) with the receptor is presented in increasing order as (5f)>(5e)>(5g)>(5a)>(5b)>(5d)>(5c)>(5i)>(5h). The structure bearing substitution as thiosemicarbazone (4), nitrogen heterocyclic (5f), halogen (5e), and azide (5g) showed good cytotoxicity activity in vitro.

Design, Synthesis and In Vitro Anti-Cancer Evaluation of Novel Derivatives of 2-(2-Methyl-1,5-diaryl-1H-pyrrol-3-yl)-2-oxo-N-(pyridin-3- yl)acetamide

2020 ◽  
Vol 16 (3) ◽  
pp. 340-349
Author(s):  
Ebrahim S. Moghadam ◽  
Farhad Saravani ◽  
Ernest Hamel ◽  
Zahra Shahsavari ◽  
Mohsen Alipour ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Peripheral Neuropathy ◽  
Cell Line ◽  
Normal Cell ◽  
Caspase 3 ◽  
Annexin V ◽  
Normal Cell Line ◽  
Anti Cancer ◽  
Mcf 7

Objective: Several anti-tubulin agents were introduced for the cancer treatment so far. Despite successes in the treatment of cancer, these agents cause toxic side effects, including peripheral neuropathy. Comparing anti-tubulin agents, indibulin seemed to cause minimal peripheral neuropathy, but its poor aqueous solubility and other potential clinical problems have led to its remaining in a preclinical stage. Methods: Herein, indibulin analogues were synthesized and evaluated for their in vitro anti-cancer activity using MTT assay (on the MCF-7, T47-D, MDA-MB231 and NIH-3T3 cell lines), annexin V/PI staining assay, cell cycle analysis, anti-tubulin assay and caspase 3/7 activation assay. Results: One of the compounds, 4a, showed good anti-proliferative activity against MCF-7 cells (IC50: 7.5 μM) and low toxicity on a normal cell line (IC50 > 100 μM). All of the tested compounds showed lower cytotoxicity on normal cell line in comparison to reference compound, indibulin. In the annexin V/PI staining assay, induction of apoptosis in the MCF-7 cell line was observed. Cell cycle analysis illustrated an increasing proportion of cells in the sub-G-1 phase, consistent with an increasing proportion of apoptotic cells. No increase in G2/M cells was observed, consistent with the absence of anti-tubulin activity. A caspase 3/7 assay protocol showed that apoptosis induction by more potent compounds was due to activation of caspase 3. Conclusion: Newly synthesized compounds exerted acceptable anticancer activity and further investigation of current scaffold would be beneficial.

scholarly journals Anti-Fibrosis Effects of Magnesium Lithospermate B in Experimental Pulmonary Fibrosis: By Inhibiting TGF-βRI/Smad Signaling

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1715
Author(s):  
Xin Luo ◽  
Qiangqiang Deng ◽  
Yaru Xue ◽  
Tianwei Zhang ◽  
Zhitao Wu ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Cell Line ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Salvia Miltiorrhiza ◽  
A549 Cells ◽  
Epithelial Cell Line ◽  
Human Lung Fibroblast ◽  
Magnesium Lithospermate B

Pulmonary fibrosis is a severe and irreversible interstitial pulmonary disease with high mortality and few treatments. Magnesium lithospermate B (MLB) is a hydrosoluble component of Salvia miltiorrhiza and has been reported to have antifibrotic effects in other forms of tissue fibrosis. In this research, we studied the effects of MLB on pulmonary fibrosis and the underlying mechanisms. Our results indicated that MLB treatment (50 mg/kg) for seven days could attenuate bleomycin (BLM)-induced pulmonary fibrosis by reducing the alveolar structure disruption and collagen deposition in the C57 mouse model. MLB was also found to inhibit transforming growth factor-beta (TGF-β)-stimulated myofibroblastic transdifferentiation of human lung fibroblast cell line (MRC-5) cells and collagen production by human type II alveolar epithelial cell line (A549) cells, mainly by decreasing the expression of TGF-β receptor I (TGF-βRI) and regulating the TGF-β/Smad pathway. Further studies confirmed that the molecular mechanisms of MLB in BLM-induced pulmonary fibrosis mice were similar to those observed in vitro. In summary, our results demonstrated that MLB could alleviate experimental pulmonary fibrosis both in vivo and in vitro, suggesting that MLB has great potential for pulmonary fibrosis treatment.

Sign in / Sign up

Export Citation Format

Share Document