scholarly journals Antiestrogenic Activity and Possible Mode of Action of Certain New Nonsteroidal Coumarin-4-acetamides

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1553 ◽  
Author(s):  
Maha S. Almutairi ◽  
Areej N. Al Suwayyid ◽  
Amal Aldarwesh ◽  
Omaima M. Aboulwafa ◽  
Mohamed I. Attia
Keyword(s):  
Breast Cancer Cell Lines ◽  
Aromatase Activity ◽  
Compound Iiib ◽  
Antiestrogenic Activity ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Diphenyl Tetrazolium Bromide ◽  
Layer Chromatography ◽  
Mcf 7

The preparation of certain 2-(2-oxo-2H-chromen-4-yl)-N-substituted acetamides IIIa–h was planned as a step in the development of new modified nonsteroidal antiestrogens. The purity of target compounds IIIa–h was checked by thin-layer chromatography (TLC), and their structures were confirmed using various spectroscopic tools including IR, 1H-NMR, 13C-NMR, and MS spectroscopy. Viability tests were applied using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effect of the synthesized compounds against two breast cancer cell lines, MCF-7 and MDA-MB-231. Compound IIIb proved the most active against MCF-7 cells, with an IC50 value of 0.32 μM. The results of an analysis of in vitro antiestrogenic activity indicated that only compound IIIb exhibited antiestrogenic activity; its IC50 value of 29.49 μM was about twice as potent as that of the reference compound, MIBP. The aromatase activity was evaluated for the synthesized target compounds IIIa–g and the intermediates Ib and IIa. A significant aromatase inhibition was observed for the intermediate Ib and compound IIIe, with IC50 values of 14.5 and 17.4 μM, respectively. Compound IIIb, namely 7-methoxy-4-(2-oxo-2-(piperidin-1-yl)ethyl)-2H-chromen-2-one, could be used as an antiestrogen and/or cytotoxic agent with selective activity against tumor cells.

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.

scholarly journals Structurally Simple Phenanthridine Analogues Based on Nitidine and Their Antitumor Activities

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 437
Author(s):  
Shu-Qin Qin ◽  
Lian-Chun Li ◽  
Jing-Ru Song ◽  
Hai-Yun Li ◽  
Dian-Peng Li
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
A549 Cells ◽  
Anticancer Activities ◽  
Human Cancer Cell Lines ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Diphenyl Tetrazolium Bromide ◽  
Conjugated Compounds

A series of novel structurally simple analogues based on nitidine was designed and synthesized in search of potent anticancer agents. The antitumor activity against human cancer cell lines (HepG2, A549, NCI-H460, and CNE1) was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro. The results showed that some of them had good anticancer activities, especially derivatives with a [(dimethylamino)ethyl]amino side chain in the C-6 position. Planar conjugated compounds 15a, 15b, and 15c, with IC50 values of 1.20 μM, 1.87 μM, and 1.19 μM against CNE1 cells, respectively, were more active than nitidine chloride. Compound 15b and compound 15c with IC50 values of 1.19 μM and 1.37 μM against HepG2 cells and A549 cells demonstrated superior activities to nitidine. Besides, compound 5e which had a phenanthridinone core displayed extraordinary cytotoxicity against all test cells, particularly against CNE1 cells with the IC50 value of 1.13 μM.

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 IN VITRO EVALUATION OF ANTICANCER POTENTIAL OF ERYTHRINA VARIEGATA L. ON BREAST CANCER CELL LINES

2017 ◽  
Vol 10 (7) ◽  
pp. 305
Author(s):  
Vaishali Rai M ◽  
Vinitha Ramanath Pai ◽  
Samuel Kevin ◽  
Herga P Kedilaya
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Morphological Changes ◽  
Treated Group ◽  
Breast Cancer Cell Lines ◽  
Liquid Chromatography Mass Spectrometry ◽  
Erythrina Variegata ◽  
Ic50 Value ◽  
Mcf 7

Objective: Species of Erythrina variegata L. is reported to be used in the treatment of cancer in traditional/folklore medicine which could be explored for their anticancer potential. We aimed to evaluate the anticancer activity of crude extracts of the leaves of E. variegata with two solvents; explore the mechanism of cytotoxicity with the effective extract and correlation with the phytochemicals in the extract.Methods: The extracts with Erythrina variegata L methanol (EVM) and chloroform (EVC) as solvents were screened for cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay on MDA-MB-231 and MCF-7 cell lines. The effective extract was further evaluated on MDA-MB-231 cells by nucleoprotein content estimation, and cell morphology was studied. High resolution liquid chromatography mass spectrometry (HRLCMS) of EVM was done to find the phytochemical composition.Results: Among the two extracts, EVM was effective at an inhibitory concentration (IC50) value of 92 μg/ml and 143 μg/ml on MCF-7 and MDA-MB-231 cells, respectively. At the IC50 value (143 μg/ml) the nucleoprotein content of the cells was 58.2%, and the apoptotic index was calculated to be 51.8%. EVM treated group showed significant morphological changes suggestive of apoptosis. HRLCMS revealed the presence of rutin, podocarpatriene, and cepharanthine which are known to be cytotoxic.Conclusion: This report is a contribution toward the validation of E. variegata as a potential source of anticancer agents.

Two New Adenosine Derivatives and their Antiproliferative Properties, an In Vitro Evaluation

2021 ◽  
Vol 21 ◽  
Author(s):  
Francisco Valdés ◽  
Bárbara Arévalo ◽  
Margarita Gutiérrez ◽  
Verónica García-Castillo ◽  
Rebeca Salgado-García ◽  
...  
Keyword(s):  
Cell Lines ◽  
In Vitro Assays ◽  
Breast Cancer Cell Lines ◽  
Antiproliferative Effects ◽  
Agonist Action ◽  
Ic50 Values ◽  
Adenosine Derivatives ◽  
High Concentrations ◽  
Mcf 7

Background: Adenosine is a natural nucleoside present in various organs and tissues, where it acts as a modulator of diverse physiological and pathophysiological processes. These actions are mediated by at least four G protein-coupled receptors, which are widely and differentially expressed in tissues. Interestingly, high concentrations of adenosine have been reported in a variety of tumors. In this context, the final output of adenosine in tumorigenesis will likely depend on the constellation of adenosine receptors expressed by tumor and stromal cells. Notably, activation of the A3 receptor can reduce the proliferative capacity of various cancer cells. Objective: The objective of this study is to describe the anti-proliferative effects of two previously synthesized adenosine derivatives with A3 agonist action (compounds 2b and 2f) through in vitro assays. Results: The antiproliferative effects of adenosine derivatives (after determining IC50 values) were comparable or even higher than those described for IB-MECA, a commercially available A3 agonist. Among possible mechanisms involved, apoptosis was found to be induced in MCF-7 cells but not in AGS or MDA-MB-231 cells. Surprisingly, we were unable to observe cellular senescence induction upon treatment with compounds 2b and 2f in any of the cell lines studied, although we cannot rule out other forms of cell cycle exit at this point. Conclusion: Both adenosine derivatives showed antiproliferative effects on gastric and breast cancer cell lines, and were able to induce apoptosis, at least in the MCF-7 cell line. Further studies will be necessary to unveil receptor specificity and mechanisms accounting for the antiproliferative properties of these novel semi-synthetic compounds.

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.

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.

(Substituted)-benzo[b]thiophene-4-carboxamide Synthesis and Antiproliferative Activity Study

2020 ◽  
Vol 17 (5) ◽  
pp. 563-573 ◽  
Author(s):  
Chandrakant Dhondiram Pawar ◽  
Dattatraya Navnath Pansare ◽  
Devanand Baburao Shinde
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Proliferative Activity ◽  
Thiophene Ring ◽  
Amide Group ◽  
Peptide Coupling ◽  
Ic50 Value ◽  
Important Building Block ◽  
Mcf 7

Background: Thiophene ring forms important building block in medicinal chemistry. Literature reveals that thiophene ring in combination with different groups shows different activity. By keeping these things in mind we have designed and synthesized a new series of amide and sulfonamide coupled thiophene. A series of novel substituted 3-sulfamoylbenzo[b]thiophene-4- carboxamide molecules containing sulfonamide and amide group were designed, synthesized and used for anti-proliferative activity study. Methods: The final compounds 16-36 were synthesized by using series of reactions comprising sulfonation, sulfonamide coupling, hydrolysis and peptide coupling. The yields of compounds 16- 36 are in the range of 90-98%. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, 13C NMR, LCMS and the purity was checked through HPLC analysis. The compounds were further tested for their in vitro anticancer activity against a series of cell lines A549, HeLa, MCF-7 and Du-145. Results: The intermediates 8-13, 15 and final compounds 16-36 were synthesized in good yields. The synthesized compounds were further tested for their anticancer activity and most of compounds showed moderate to good anticancer activity against all four cell lines. Conclusion: We have synthesized 21 compounds and were screened for anticancer activity against MCF-7, HeLa, A-549 and Du-145 cancer cell lines. Most of the compounds were active for tested cell lines with IC50 value in the range of 1.81 to 9.73 μM. The compounds 18, 19, 21, 25, 30, 31 and 33 are most active in cell line data with IC50 value in the range of 1.81 to 2.52 μM.

New Ferrocene Compounds as Selective Cyclooxygenase (COX-2) Inhibitors: Design, Synthesis, Cytotoxicity and Enzyme-inhibitory Activity

2018 ◽  
Vol 18 (2) ◽  
pp. 295-301 ◽  
Author(s):  
Shabnam Farzaneh ◽  
Elnaz Zeinalzadeh ◽  
Bahram Daraei ◽  
Soraya Shahhosseini ◽  
Afshin Zarghi
Keyword(s):  
Cell Lines ◽  
Inhibitory Activity ◽  
Fibroblast Cell ◽  
Breast Cancer Cell Lines ◽  
Ferrocene Derivatives ◽  
Cox 2 ◽  
Cytotoxicity Effects ◽  
Cox 2 Inhibitors ◽  
Mcf 7

Background: Due to the astonishing properties of ferrocene and its derivatives, it has a broad application in diverse areas. Numerous ferrocene derivatives demonstrated anti-proliferative activity. Also COX-2, as a key isoenzyme for production of prostaglandins, is frequently overexpressed in various cancers. It is now recognized that COX-2 over expression promotes tumorigenic functions which can be suppressed by COX-2 inhibitors, a phenomenon useful for the preventing of tumor progression. The combination of COX-2 inhibitors with other anti-cancer or cancer prevention drugs may reduce their side effects in future cancer prevention and treatment. Objective: Owing to high anticancer potential of ferrocene derivatives and considerable COX-2 inhibitory and cytotoxicity effects of our previously synthesized chalcones, we decided to incorporate the ferrocenyl moiety into appropriate COX-2 inhibitor chalcone based scaffold, to evaluate COX-2 inhibitory activity as well as anticancer activities. Methods: Chalcones were synthesized via clasien-schmidt condensation of methylsulfonyl aldehyde and acetyl ferrocene. Further different amines with solvent free and ultra sound condition were reacted with chalcones to have different 1-ferrocenyl-3-amino carbonyl compounds. Docking study was carried out with Auto Dock vina software. All the newly-synthesized compounds were evaluated for their cyclooxygenase-2 (COX-2) inhibitory activity using chemiluminescent enzyme assays as well as cytotoxicity activity against MCF-7 and T47D and fibroblast cell lines by MTT assay. Results: In vitro COX-1/COX-2 inhibition studies demonstrated that all compounds were selective inhibitors of the COX-2 isozyme with IC50 values in the highly potent 0.05-0.12 µM range, and COX-2 selectivity indexes (SI) in the 148.3-313.7 range. These results indicated that either potency or selectivity of COX-2 inhibitory activity was affected by the nature and size of the substituents on C-3 of propane-1-one. Also anti-proliferative and toxicity activities of synthesized compounds against breast cancer cell lines MCF-7 and T47D and fibroblast cell lines showed that the synthesized compounds had mild to moderate cytotoxicity against MCT7 and T47D breast cancer cell lines at 10 µM concentration. In vitro COX-1/COX-2 inhibition studies and anticancer activity against MCF-7, identified 1-ferrocenyl-3-(4-methylsulfonylphenyl) propen-1-one as a potent compound (IC50 COX-2 = 0.05 µM, MCF-7: % inhibition (at concentration of 10 µM) = 32.7%), and also 1-ferrocenyl-3- (propan-1-amine)-3-(4-methylsulfonylphenyl) propan-1-one showed the most selectivity on COX-2 inhibition (selectivity index= 313.7). Conclusion: A novel group of ferrocene compounds, possessing a methyl sulfonyl COX-2 pharmacophore were synthesized to investigate the effect of different substituents on selectivity and potency of COX-2 inhibitory activity and their cytotoxicity effects. This study indicates that 1-ferrocenyl-3-amino carbonyl compounds having ferrocene motif and methyl sulfonyl COX-2 pharmacophore is a suitable scaffold to design COX-2 inhibitors and anti-cancer agents.

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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