scholarly journals In Vitro Evaluation and Docking Studies of 5-oxo-5H-furo[3,2-g]chromene-6-carbaldehyde Derivatives as Potential Anti-Alzheimer’s Agents

2019 ◽  
Vol 20 (21) ◽  
pp. 5451
Author(s):  
Malose J. Mphahlele ◽  
Samantha Gildenhuys ◽  
Emmanuel N. Agbo
Keyword(s):  
Breast Cancer ◽  
Biological Activity ◽  
Active Sites ◽  
Kinetic Studies ◽  
Inhibitory Effect ◽  
Docking Studies ◽  
Significant Inhibitory Effect ◽  
Anti Oxidant ◽  
Mcf 7

A series of novel 2-carbo–substituted 5-oxo-5H-furo[3,2-g]chromene-6-carbaldehydes and their 6-(4-trifluoromethyl)phenylhydrazono derivatives have been prepared and evaluated for biological activity against the human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The most active compounds from each series were, in turn, evaluated against the following enzyme targets involved in Alzheimer’s disease, β-secretase (BACE-1) and lipoxygenase-15 (LOX-15), as well as for anti-oxidant potential. Based on the in vitro results of ChE and β-secretase inhibition, the kinetic studies were conducted to determine the mode of inhibition by these compounds. 2-(4-Methoxyphenyl)-5-oxo-5H-furo[3,2-g]chromene-6-carbaldehyde (2f), which exhibited significant inhibitory effect against all these enzymes was also evaluated for activity against the human lipoxygenase-5 (LOX-5). The experimental results were complemented with molecular docking into the active sites of these enzymes. Compound 2f was also found to be cytotoxic against the breast cancer MCF-7 cell line.

scholarly journals Synthesis and Evaluation of the 4-Substituted 2-Hydroxy-5-Iodochalcones and Their 7-Substituted 6-Iodoflavonol Derivatives for Inhibitory Effect on Cholinesterases and β-Secretase

2018 ◽  
Vol 19 (12) ◽  
pp. 4112 ◽  
Author(s):  
Malose Mphahlele ◽  
Emmanuel Agbo ◽  
Samantha Gildenhuys
Keyword(s):  
Kinetic Studies ◽  
Inhibitory Effect ◽  
Docking Studies ◽  
Significant Inhibition ◽  
Strong Interactions ◽  
Protein Residues ◽  
Significant Inhibitory Effect ◽  
Increased Activity ◽  
Bace 1

A series of 2-aryl-3-hydroxy-6-iodo-4H-chromen-4-ones substituted at the 7-position with a halogen atom (X = F, Cl and Br) or methoxy group and their corresponding 4-substituted 2-hydroxy-5-iodochalcone precursors were evaluated in vitro for inhibitory effect against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-secretase (BACE1) activities. Although moderate inhibitory effect was observed for the chalcones against AChE, derivatives 2h, 2j and 2n exhibited significant inhibitory effect against BChE and BACE-1. The 2-aryl-7-fluoro-8-iodoflavonols 3b and 3c, on the other hand, exhibited increased activity and selectivity against AChE and reduced effect on BACE-1. The flavonols 3h, 3i, 3k, 3l and 3p exhibited moderate inhibitory effect against AChE, but significant inhibition against BChE. Compounds 2j and 3l exhibited non-competitive mode of inhibition against BACE-1. Molecular docking predicted strong interactions with the protein residues in the active site of BACE-1 implying these compounds bind with the substrate. Similarly docking studies predicted interaction of the most active compounds with both CAS and PAS of either AChE or BChE with mixed type of enzyme inhibition confirmed by kinetic studies.

Computational Druglikeness Assessment, Synthesis, Characterization and in vitro Biological Activity Evaluation of some Novel Mixed Metal Complexes of 2-(butan-2-ylidene) hydrazinecarbothioamide

2020 ◽  
Vol 23 ◽  
Author(s):  
Tahmeena Khan ◽  
Iqbal Azad ◽  
Alfred J. Lawrence ◽  
Saman Raza ◽  
Seema Joshi ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Biological Activity ◽  
Molecular Docking ◽  
Metal Complexes ◽  
Docking Studies ◽  
Mixed Metal ◽  
Ic50 Value ◽  
Mixed Metal Complexes ◽  
Mcf 7

Aims and Objectives: The heteronuclear (mixed metal) complexes of Schiff bases have been explored as part of the coordination and bioinorganic chemistry. Five novel mixed metal complexes of (E)-2-(butan-2-ylidene) hydrazinecarbothioamide (2-butanone thiosemicarbazone) were prepared and characterized by different spectroscopic techniques. Molecular docking studies were performed with three proteins for two complexes. The toxicity potential, physicochemical properties and bioactivity scores were also predicted. The complexes were tested against three cell lines and also evaluated for their antibacterial activity. Materials and Methods: The mixed metal complexes were prepared in 1:4 molar ratio of metal salt and ligand. OSIRIS 4.6.1 was used to assess the toxicity whereas Molinspiration 2016.03 was used to calculate the bioactivity scores and other physicochemical properties. Principal Component Analysis (PCA) was performed using the Osiris Property Explorer 4.5.1 for defining and visualizing multidimensional property spaces by assigning dimensions to numerical descriptors. Molecular docking studies were performed with three proteins. The anticancer activity was tested against MCF-7, MDA-MB-231, HepG2 and A549 cell lines using MTT assay whereas antibacterial activity was tested using disc diffusion method. Results and Conclusion: The melting points of the complexes were as high as >3500C, indicating high thermal stability. [CuZn(C5H11N3S)4(SO4)2] exhibited minimum energies against the selected proteins. The bioactivity scores of the complexes were between -0.50 and 0.0. All the prepared complexes showed negative Ames score predicted their non-carcinogenic nature. Against A549 [CuZn(C5H11N3S)4(SO4)2], [CoZn(C5H11N3S)4(SO4)Cl2] and [FeZn(C5H11N3S)4(SO4)2] showed potential in vitro activity. IC50 of these three complexes were 19.69, 37.73 and 38.4 respectively. Against MCF-7, [FeCu(C5H11N3S)4(SO4)2] had IC50 value 53.5. Whereas, against HepG2 [CoZn(C5H11N3S)4(SO4)Cl2] was active having IC50 value 61.8. [CoZn(C5H11N3S)4(SO4)Cl2], [FeCu(C5H11N3S)4(SO4)2] and [FeCo(C5H11N3S)4(SO4)Cl2] were active against S. aureus in the concentration range 2-20 mg/mL. The complexes showed improved biological activity as compared to the monometallic complexes of the same ligand.

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.

Development of Furo[2,3-b]quinoline Derivatives with Anti-Breast Cancer Property by Targeting Topoisomerase II

2020 ◽  
Vol 20 ◽  
Author(s):  
Ying Wang ◽  
Na Li ◽  
Neng Jiang ◽  
Li Chen ◽  
Jianbo Sun
Keyword(s):  
Breast Cancer ◽  
Topoisomerase Ii ◽  
Inhibitory Effect ◽  
Normal Breast ◽  
Quinoline Derivative ◽  
Breast Cancer Cell Lines ◽  
Quinoline Derivatives ◽  
Substituted Anilines ◽  
Mcf 7

Abstract:: A number of novel furo[2,3-b]quinoline derivatives were designed and synthesized by introducing different substituted anilines and phenols to C4-position of furo[2,3-b]quinoline. All target compounds were evaluated in vitro against two human breast cancer cell lines (MCF-7 and MDA-MB-231) and one normal breast cell (MCF-10A) by MTT (3-[4,5-dimethylthylthiazol-2-yl]-2,5 diphenyltetrazolium broide, Thiazolyl blue) method. Most derivatives showed significant cytotoxic activity on the two breast cancer cells with IC50 values in the range of (5.60-26.24 μM) and a certain selectivity, especially in the inhibition of MDA-MB-231. More notably, they were less toxic to normal breast cell (MCF-7-10A). Compound I7 could be considered as ideal selective candidate for further study. Mechanism studies showed that I7 could inhibit the proliferation of cells by arresting MDA-MB-231 cell cycle at G2/M phase. Overall, as a novel furo[2,3-b]quinoline derivative, I7 exhibited excellent inhibitory effect in MDA-MB-231 cell and was worthy of in-depth study.

scholarly journals Metformin Decreases 2-HG Production through the MYC-PHGDH Pathway in Suppressing Breast Cancer Cell Proliferation

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 480
Author(s):  
Sehyun Oh ◽  
Young-Up Cho ◽  
Minsun Chang ◽  
Sunghyouk Park ◽  
Hyuknam Kwon
Keyword(s):  
Breast Cancer ◽  
Inhibitory Effect ◽  
Anticancer Effect ◽  
Isocitrate Dehydrogenase 1 ◽  
Growth Inhibitory Activity ◽  
Tumorigenic Mechanism ◽  
Cancer Tissues ◽  
Mcf 7

The biguanide drug metformin has been widely used for the treatment of type 2 diabetes, and there is evidence supporting the anticancer effect of metformin despite some controversy. Here, we report the growth inhibitory activity of metformin in the breast cancer (MCF-7) cells, both in vitro and in vivo, and the associated metabolic changes. In particular, a decrease in a well-known oncometabolite 2-hydroxyglutarate (2-HG) was discovered by a metabolomics approach. The decrease in 2-HG by metformin was accompanied by the reduction in histone methylation, consistent with the known tumorigenic mechanism of 2-HG. The relevance of 2-HG inhibition in breast cancer was also supported by a higher level of 2-HG in human breast cancer tissues. Genetic knockdown of PHGDH identified the PHGDH pathway as the producer of 2-HG in the MCF-7 cells that do not carry isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) mutations, the conventional producer of 2-HG. We also showed that metformin’s inhibitory effect on the PHGDH-2HG axis may occur through the regulation of the AMPK-MYC pathway. Overall, our results provide an explanation for the coherent pathway from complex I inhibition to epigenetic changes for metformin’s anticancer effect.

scholarly journals The synergistic anticancer traits of graphene oxide plus doxorubicin against BT474 and MCF7 breast cancer stem cells in vitro

2021 ◽  
Author(s):  
Mahsa Ebrahimi ◽  
maryam teimouri ◽  
Mehdi Pooladi
Keyword(s):  
Breast Cancer ◽  
Graphene Oxide ◽  
Cell Lines ◽  
Colony Formation ◽  
Inhibitory Effect ◽  
Control Group ◽  
Mcf7 Cells ◽  
Mtt Test ◽  
Mcf 7

Abstract Breast cancer is among leading causes of death due to cancers around the globe. Current therapeutic approaches towards healing of breast cancer have been associated with poor outcomes. Graphene and its derivatives have a two-dimensional flat structure, which is characterized by the ability to carry drugs and modify the surface, low cytotoxicity and high biocompatibility. This study was performed on MCF7 and BT474 human breast cancer cells. Different concentrations of doxorubicin (DOX), graphene oxide (GO) and graphene oxide plus doxorubicin (GO-DOX) were subjected to both cell lines at specified intervals. At the end of the treatments, MTT test was applied to determine the viability of cells and then flow cytometry, colony formation and spheroid tests were implemented for both cell lines treated with DOX, GO and GO-DOX components. We used DLS and TEM to confirm the GO properties. According to the MTT test results, 1 µL of DOX at 10 mg /mL (equivalent to 0.1 mg / mL) caused 50% survival of MCF7 cells at 24 hours. In both cell lines, an increase in apoptosis occurred after incubation with GO and DOX. Although, a rate of mortality of MCF-7 cells was due to necrosis, the BT474 cells death was merely through the apoptosis. Furthermore, the results of colony formation test outlined an enhancing inhibitory effect in the presence of GO-DOX as a comparison to the control. Additionally, spheroids formed following treatment with GO-DOX exhibited a significant decrease compared to their control group; with an increase in the number of spheroids in BT474 cells compared to those in the MCF-7. The decreasing effect of compounds against the migration and cell invasion potential was also observed, being higher in MCF7 than BT474 cells. The effects of cytotoxic GO were observed at higher concentrations.

scholarly journals Bioinformatics, Molecular Docking and Experiments In Vitro Analyze the Prognostic Value of CXC Chemokines in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Fei Wang ◽  
Chong Yuan ◽  
He-Zhen Wu ◽  
Bo Liu ◽  
Yan-Fang Yang
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Prognostic Value ◽  
Public Health Problem ◽  
Inhibitory Effect ◽  
Major Public Health Problem ◽  
Normal Tissues ◽  
Incidence And Mortality ◽  
Mcf 7

The increasing incidence and mortality rate of Breast cancer (BC) make it a major public health problem around the world. CXC chemokines can mediate the migration of immune cells and regulate apoptosis in tumor. However, the expression and prognostic value of them in BC and their targeted drugs have not been clarified. Therefore, in this study, ONCOMINE, GEPIA2.0, UALCAN, Venny2.1.0, cBioPortal, STRING, Gene MANIA, Pathway Commons, DAVID6.8, Omicshare, Cytoscape3.6.1, TIMER2.0, Drug Bank, TCMSP, RSCBPDB, PubChem, pkCSM, Chem Draw, AutoDockTools-1.5.6 and PyMOL were utilized for analysis. The expression of CXCL1-3, CXCL9-13 between BC and normal tissues was significantly different in all the three databases. And the expression of CXCL1-2, CXCL12-13 was correlated with the stages of BC. But only CXCL1-3 were prone to mutation, and negatively correlated with survival and prognosis of BC patients. Taken together, CXCL1-2 might be therapeutic targets and biomarkers for BC patients. In addition, both of them were associated with immune infiltration. The results of molecular docking showed that Quercetin was most likely to be developed as drugs that interacted directly with CXCL1-2. And GLU29 of CXCL1, ASP-1, PRO-96, TRP-47 and LEU-45 of CXCL2 were the most potential sites, which provided valuable reference for further study of pharmacodynamics and mechanism. In addition, the inhibitory effect of Quercetin on proliferation and promoting apoptosis of BC related cell lines were confirmed in vitro. Western blot and Real-Time PCR confirmed that it increased the expression of CXCL1-2 in MDA-MB-231 and MCF-7 cells.

scholarly journals INSILICO DESIGN, SYNTHESIS AND CHARACTERIZATION OF SOME NOVEL BENZOTHIAZOLE DERIVATIVES AS ANTI-CANCER AGENTS

2017 ◽  
Vol 10 (4) ◽  
pp. 150
Author(s):  
Leena K Pappachen ◽  
Subin Mary Zachariah ◽  
Deepthy Chandran
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Docking Studies ◽  
Design Synthesis ◽  
Standard Drug ◽  
Mass Spectral ◽  
Benzothiazole Derivatives ◽  
Anti Cancer ◽  
Mcf 7

Objectives: Cancer is a disease characterized by uncontrollable, irreversible, independent, autonomous, uncoordinated and relatively unlimited and abnormal over growth of tissues. Breast cancer is the second most common type of cancer after lung cancer. The aim of the study is to carry out the docking studies, synthesis and anti-tumour activities  of Benzothiazole derivatives containing oxadiazole groups or amino groups.Methods: The docking studies of benzothiazole derivatives were done with known anti-cancer targets like oestrogen receptor by using argus lab and auto dock programmes with the standard drug tamoxifen. Based upon  the results obtained from the molecular modeling, the derivatives were selected for the synthesis. The synthesized compounds were characterized by melting point, TLC, IR, 1H NMR, 13CNMR, MASS spectral data and screened for their in- vitro anti-cancer activities.Results: The docking scores obtained for benzothiazole derivatives (BT1,BT2,BT3,BT4) and std.tamoxifen  from the preliminary docking program by using  argusLab  were- 9.68,-9.4,-9.59, -11.1988,-9.71 and  by using autodock program were -6.29, -5.25,-7.19,-7.48,-3.86 respectively. All the four derivatives were synthesized, characterized and subjected to in vitro anticancer screening by MTT assay in breast cancer (MCF-7) cell lines. Compounds DBT1, DBT2, DBT3 were the most active compounds against MCF-7 cell lines with IC50 of 70.0, 64.0 and 65.0, respectively.Conclusion: All the four  derivatives show  good docking scores when compared to standard drug and can be concluded that all the synthesized benzothiazole  ligands show good anti-cancer property.Keywords: Benzothiazole, Oxadiazole, Estrogen receptor, Anticancer targets.

Synthesis and preliminary in vitro biological activity of non-steroidal cytotoxic estrogens designed for the treatment of breast cancer

1993 ◽  
Vol 71 (9) ◽  
pp. 1327-1333 ◽  
Author(s):  
G. Bérubé ◽  
P. Wheeler ◽  
C.H.J. Ford ◽  
M. Gallant ◽  
Z. Tsaltas
Keyword(s):  
Breast Cancer ◽  
Biological Activity ◽  
Chemotherapeutic Agents ◽  
Target Cells ◽  
Human Breast ◽  
Breast Tumor Cell ◽  
Human Breast Tumor ◽  
Development Of Resistance ◽  
Mcf 7

The development of resistance to endocrine therapy as well as chemotherapy is presently a major problem in the treatment of breast cancer. To minimize this obstacle, new, more selective and potent, chemotherapeutic agents should be designed. One way to improve selectivity is to link a cytotoxic moiety to a molecule possessing an affinity to the estrogen receptor (ER). The latter would be used to direct the cytotoxic portion of the molecule towards the target cells. Our initial approach led us to the synthesis of new triphenylethylene–platinum(II) complexes 1a–c. The commercially available desoxyanisoin (10) was efficiently transformed in seven steps into the platinum(II) complexes 1a–c with an overall yield exceeding 30%. The biological activity of compounds 1a–c was evaluated in vitro on ER+ and ER− human breast tumor cell lines: MCF-7 and MDA-MD-231.

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