scholarly journals A Nitrocarbazole as a New Microtubule-Targeting Agent in Breast Cancer Treatment

2021 ◽  
Vol 11 (19) ◽  
pp. 9139
Author(s):  
Maria Stefania Sinicropi ◽  
Cinzia Tavani ◽  
Camillo Rosano ◽  
Jessica Ceramella ◽  
Domenico Iacopetta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Activity ◽  
Breast Cancer Cell Lines ◽  
Cellular Functions ◽  
Anticancer Properties ◽  
Cycle Arrest ◽  
In Silico Studies ◽  
Ic50 Values ◽  
Mcf 7

Breast cancer is still considered a high-incidence disease, and numerous are the research efforts for the development of new useful and effective therapies. Among anticancer drugs, carbazole compounds are largely studied for their anticancer properties and their ability to interfere with specific targets, such as microtubule components. The latter are involved in vital cellular functions, and the perturbation of their dynamics leads to cell cycle arrest and subsequent apoptosis. In this context, we report the anticancer activity of a series of carbazole analogues 1–8. Among them, 2-nitrocarbazole 1 exhibited the best cytotoxic profile, showing good anticancer activity against two breast cancer cell lines, namely MCF-7 and MDA-MB-231, with IC50 values of 7 ± 1.0 and 11.6 ± 0.8 μM, respectively. Furthermore, compound 1 did not interfere with the growth of the normal cell line MCF-10A, contrarily to Ellipticine, a well-known carbazole derivative used as a reference molecule. Finally, in vitro immunofluorescence analysis and in silico studies allowed us to demonstrate the ability of compound 1 to interfere with tubulin organization, similarly to vinblastine: a feature that results in triggering MCF-7 cell death by apoptosis, as demonstrated using a TUNEL assay.

Design, Synthesis, In Silico and In Vitro Evaluation of Novel Pyrimidine Derivatives as EGFR Inhibitors

2020 ◽  
Vol 20 ◽  
Author(s):  
Gurubasavaraja S.P. Matada ◽  
Nahid Abbas ◽  
Prasad S. Dhiwar ◽  
Rajdeep Basu ◽  
Giles Devasahayam
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Anticancer Activity ◽  
In Silico ◽  
Docking Studies ◽  
Breast Cancer Cell Lines ◽  
Pyrimidine Derivatives ◽  
Molecular Docking Studies ◽  
Mcf 7

Background: The abnormal signaling from tyrosine kinase causes many types of cancers namely breast cancer, non-small cell lung cancer, and chronic myeloid leukemia. This research reports the in-silico, synthesis, and in-vitro study of novel pyrimidine derivatives as EGFR inhibitors. Objective: The objective of the research study is to discover more promising lead compounds using drug discovery process, in which the rational drug design is achieved by the molecular docking and virtual pharmacokinetic studies. Methods: The molecular docking studies were carried out using discovery studio 3.5-version software. The molecules with good docking and binding energy score were synthesized as well as their structures were confirmed by FT-IR, NMR, Mass and elemental analysis. Subsequently molecules were evaluated for their anticancer activity using MDA-MB-231, MCF-7 and A431 breast cancer cell lines by MTT and tyrosine kinase assay methodology. Results: Pyrimidine derivatives displayed anticancer activity. Particularly, compound R8 shows significant cytotoxicity against MDA-MB-231 with an IC50 18.5 ± 0.6 µM. Molecular docking studies proved that the compound R8 has good binding fitting by forming hydrogen bonds with amino acid residues at ATP binding sites of EGFR. Conclusion: Eight pyrimidine derivatives were designed, synthesized and evaluated against breast cancer cell lines. Compound R8 significantly inhibited the growth of MDA-MB-231 and MCF-7. Molecular docking studies reveled that compound R8 has good fitting by forming different Hydrogen bonding interactions with amino acids at ATP binding site of epidermal growth factor receptor target. Compound R8 was a promising lead molecule that showed better results as compared to other compounds in in-vitro studies.

Synthesis and In Vitro Evaluation of Tetrahydroquinoline Derivatives as Antiproliferative Compounds of Breast Cancer via Targeting the GPER

2019 ◽  
Vol 19 (6) ◽  
pp. 760-771 ◽  
Author(s):  
Oscar J. Zacarías-Lara ◽  
David Méndez-Luna ◽  
Gustavo Martínez-Ruíz ◽  
José R. García-Sanchéz ◽  
Manuel J. Fragoso-Vázquez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
In Silico ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
In Silico Studies ◽  
Mcf 7

Background: Some reports have demonstrated the role of the G Protein-coupled Estrogen Receptor (GPER) in growth and proliferation of breast cancer cells. Objective: In an effort to develop new therapeutic strategies against breast cancer, we employed an in silico study to explore the binding modes of tetrahydroquinoline 2 and 4 to be compared with the reported ligands G1 and G1PABA. Methods: This study aimed to design and filter ligands by in silico studies determining their Lipinski's rule, toxicity and binding properties with GPER to achieve experimental assays as anti-proliferative compounds of breast cancer cell lines. Results: In silico studies suggest as promissory two tetrahydroquinoline 2 and 4 which contain a carboxyl group instead of the acetyl group (as is needed for G1 synthesis), which add low (2) and high hindrance (4) chemical moieties to explore the polar, hydrophobic and hindrance effects. Docking and molecular dynamics simulations of the target compounds were performed with GPER to explore their binding mode and free energy values. In addition, the target small molecules were synthesized and assayed in vitro using breast cancer cells (MCF-7 and MDA-MB-231). Experimental assays showed that compound 2 decreased cell proliferation, showing IC50 values of 50µM and 25µM after 72h of treatment of MCF-7 and MDA-MB-231 cell lines, respectively. Importantly, compound 2 showed a similar inhibitory effect on proliferation as G1 compound in MDA-MB-231 cells, suggesting that both ligands reach the GPER-binding site in a similar way, as was demonstrated through in silico studies. Conclusion: A concentration-dependent inhibition of cell proliferation occurred with compound 2 in the two cell lines regardless of GPER.

scholarly journals Biotinylated xanthohumol: synthesis and in vitro biological evaluation for anticancer therapy

2018 ◽  
Author(s):  
Monika Stompor ◽  
Rafał Podgórski ◽  
Marta Świtalska ◽  
Joanna Wietrzyk
Keyword(s):  
Breast Cancer ◽  
Antioxidant Activity ◽  
Cancer Cells ◽  
Cell Lines ◽  
Biological Evaluation ◽  
Breast Cancer Cell Lines ◽  
Dpph Method ◽  
Ic50 Values ◽  
Mcf 7

Two biotinylated derivatives of the main hop chalcone xanthohumol (1) were prepared by a one-step synthesis via esterification using biotin and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC HCl) and 4-dimethylaminopyridine (DMAP) as coupling reagents. The products were characterized spectroscopically and their antiproliferative activity toward MCF-7, MCF-10A, HepG2, MDA-MB-231, 4T1 and Balb/3T3 cell lines was investigated using the SRB assay. For all three tested compounds the best activity was noted in the case of human (MCF-7) and mice (4T1) breast cancer cell lines (IC50 values < 9 μM). Both biotinylated derivatives showed higher anticancer activity than xanthohumol (1) towards all types of tested breast cancer cells. Double biotinylated xanthohumol (3) proved to be the most active in inhibiting cell growth, with IC50 values equal to 5.35 ± 1.5 μM for 4T1 and 8.03 ± 0.53 µM for MCF-7 cell lines. Compound 3 was also more active than 1 and 2 against liver cancer cells HepG2 (IC50 = 17.37 ± 5.1 μM), while the IC50 values for 1 and 2 were equal to 21.5 ± 2.7 and 22.1 ± 3.9 µM, respectively. 4‑O‑biotinylxanthohumol (2) was the second most active growth inhibitor, particularly with respect to MCF-7 (IC50 = 6.19 ± 1.7 μM) and 4T1 (IC50 = 6.64 ± 0.4 μM) cell lines. The antioxidant activity was evaluated using the 1.1-diphenyl-2-picrylhydrazyl radical (DPPH) method. All tested compounds (1-3) have antioxidant activity between 2.73 and 3.38 mM. It was reported for the first time that new prenylated chalcones containing the biotin moiety effectively inhibited proliferation of cancer cells in vitro.

scholarly journals Myrtus comunis and Eucalyptus camaldulensis cytotoxicity on breast cancer cells

2012 ◽  
pp. 65-73 ◽  
Author(s):  
Jelena Hrubik ◽  
Sonja Kaisarevic ◽  
Branka Glisic ◽  
Emilija Jovin ◽  
Neda Mimica-Dukic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Eucalyptus Camaldulensis ◽  
In Vitro Cytotoxicity ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Significant Difference ◽  
Ic50 Values ◽  
Eucalyptus Camaldulensis Dehnh ◽  
Mcf 7

In vitro cytotoxicity of methanol, ethyl acetate, n-buthanol, and water extracts of Myrtus communis L. and Eucalyptus camaldulensis Dehnh. was examined against two human breast cancer cell lines (MCF 7 and MDA-MB-231) using MTT and SRB assays. The results showed significant cytotoxic potential of examined extracts, with IC50 values ranging from 7 to 138 ?g/ml for M. communis and 3-250 ?g/ml for E. camaldulensis. The two plants generally expressed similar activity, and no significant difference in cell line?s sensitivity towards extracts was observed. The results indicate to M. communis and E. camaldulensis as candidates for thorough chemical analyses for identification of active compounds, and eventually for attention in the process of discovery of new natural products in the control of cancer.

scholarly journals PGMD/curcumin nanoparticles for the treatment of breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mankamna Kumari ◽  
Nikita Sharma ◽  
Romila Manchanda ◽  
Nidhi Gupta ◽  
Asad Syed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Activity ◽  
Entrapment Efficiency ◽  
Breast Cancer Cell Lines ◽  
Dapi Staining ◽  
Scratch Assay ◽  
Curcumin Nanoparticles ◽  
Dodecanedioic Acid ◽  
Mcf 7

AbstractThe present study aims at developing PGMD (poly-glycerol-malic acid-dodecanedioic acid)/curcumin nanoparticles based formulation for anticancer activity against breast cancer cells. The nanoparticles were prepared using both the variants of PGMD polymer (PGMD 7:3 and PGMD 6:4) with curcumin (i.e. CUR NP 7:3 and CUR NP 6:4). The size of CUR NP 7:3 and CUR NP 6:4 were found to be ~ 110 and 218 nm with a polydispersity index of 0.174 and 0.36, respectively. Further, the zeta potential of the particles was − 18.9 and − 17.5 mV for CUR NP 7:3 and CUR NP 6:4, respectively. The entrapment efficiency of both the nanoparticles was in the range of 75–81%. In vitro anticancer activity and the scratch assay were conducted on breast cancer cell lines, MCF-7 and MDA-MB-231. The IC50 of the nanoformulations was observed to be 40.2 and 33.6 μM at 48 h for CUR NP 7:3 and CUR NP 6:4, respectively, in MCF-7 cell line; for MDA-MB-231 it was 43.4 and 30.5 μM. Acridine orange/EtBr and DAPI staining assays showed apoptotic features and nuclear anomalies in the treated cells. This was further confirmed by western blot analysis that showed overexpression of caspase 9 indicating curcumin role in apoptosis.

scholarly journals The influence of a single and double biotinylation of xanthohumol on its anticancer activity

2019 ◽  
Author(s):  
Monika Stompor ◽  
Marta Świtalska ◽  
Joanna Wietrzyk
Keyword(s):  
Breast Cancer ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Lines ◽  
Growth Inhibitor ◽  
Breast Cancer Cell Lines ◽  
Active Growth ◽  
Ic50 Values ◽  
4T1 Breast Cancer ◽  
Mcf 7

Two biotinylated derivatives of the main hop chalcone xanthohumol (1) were prepared by a one-step synthesis via esterification using biotin and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC×HCl) and 4-dimethylaminopyridine (DMAP) as coupling reagents. The products were characterized spectroscopically and their antiproliferative activity toward MCF-7, MCF-10A, HepG2, MDA-MB-231, 4T1 and Balb/3T3 cell lines was investigated using the SRB assay. For all three tested compounds the best activity was noted in the case of human (MCF-7) and mice (4T1) breast cancer cell lines (IC50 values < 9 μM). Both biotinylated derivatives showed slightly higher anticancer activity than xanthohumol (1) towards all types of tested breast cancer cells. Double biotinylated xanthohumol (3) proved to be the most active in inhibiting cell growth, with IC50 values equal to 5.35 ± 1.5 μM for 4T1 and 8.03 ± 0.53 µM for MCF-7 cell lines. Compound 3 was also more active than 1 and 2 against liver cancer cells HepG2 (IC50 = 17.37 ± 5.1 μM), while the IC50 values for 1 and 2 were equal to 21.5 ± 2.7 and 22.1 ± 3.9 µM, respectively. 4‑O‑biotinylxanthohumol (2) was the second most active growth inhibitor, particularly with respect to MCF-7 (IC50 = 6.19 ± 1.7 μM) and 4T1 (IC50 = 6.64 ± 0.4 μM) cell lines. Our preliminary study on biotinylated xanthohumol (1) have shown that this type of functionalization is an effective method for the production of active biomolecules and study on this area should be continued thereby extending their applications.

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.

Cytotoxic Constituents from the Bark of Erythrina poeppigiana Against the MCF-7 Breast Cancer Cell Lines

2020 ◽  
Vol 10 (3) ◽  
pp. 257-261
Author(s):  
Tati Herlina ◽  
Merlin ◽  
Mohd. Azlan ◽  
Unang Supratman
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Chemical Structure ◽  
Breast Cancer Cell Lines ◽  
Erythrina Poeppigiana ◽  
Structure Activity ◽  
Cancer Line ◽  
Cytotoxic Compounds ◽  
Ic50 Values ◽  
Mcf 7

Background: Erythrina poeppigiana (Leguminosae) is a high-growing plant with an orange flower that is widely distributed in tropical and subtropical countries. This particular plant is widely used in traditional medicine for gynecological complications and the treatment of various diseases. There exists no previous information regarding cytotoxic compounds from this plant. Objective: This research is to isolate cytotoxic compounds from E. poeppigiana. Methods: The isolation step was carried out using a combination of chromatographic techniques to obtain isolated three compounds (1, 2, and 3). Results: The chemical structure of isolated compounds was elucidated by spectroscopic methods and identified as β-erythroidine (1), 8-oxo-β-erythroidine (2), and 8-oxo-α-erythroidine (3). Compounds (1-3) showed cytotoxic activity against MCF-7 breast cancer line with IC50 values of 36.8, 60.8 and 875.4 μM, respectively. Conclusion: Three compounds have been successfully isolated from Erythrina poeppigiana (Leguminosae), showing cytotoxic properties against MCF-7 breast cancer line. Structure-activity relationship studies showed that the presence of enone moiety on compound 1 can reduce its cytotoxic activity towards MCF-7 breast cancer line.

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