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Ru(H2dtpa) (H2O) and Pd (DME)Cl2 were prepared, and their structures were confirmed by different structural tools. [Ru(H4dtpa) (cysteine)] Cl was separated as a model for the interaction of Ru (III) complex containing DTPA ligand with its corresponding most active amino acid and the geometrical parameters for the ternary complex and their constituent ligands are evaluated. Cytotoxicity was examined for both complexes against different cancer cell lines (HCT116, A549 and Mcf7). They were tested against a normal human lung cell line (W138). In addition, both complexes ensured cytocidal, not cytostatic effect. Several molecular tools were utilized in order to figure out the mechanism of action that two complexes followed to inhibit human colon cancer (HCT116) cell line. Gene expression analysis, cell cycle assay, genomic DNA analysis, and apoptosis were a molecular techniques that proved both Ru(H2dtpa) (H2O) and Pd (DME)Cl2 complexes were promising and effective chemotherapeutic agents against colon carcinoma in this current study. So, authors recommended more in vivo future studies should be done to make sure of complexes bioactivity and safety before they would be used commercially. [ABSTRACT FROM AUTHOR]

Chalcones are interesting anticancer drug candidates which have attracted much interest due to their unique structure and their extensive biological activity. Various functional modifications in chalcones have been reported, along with their pharmacological properties. In the current study, novel chalcone derivatives with the chemical base of tetrahydro-[1,2,4]triazolo[3,4-a]isoquinolin-3-yl)-3-arylprop-2-en-1-one were synthesized, and the structure of their molecules was confirmed through NMR spectroscopy. The antitumor activity of these newly synthesized chalcone derivatives was tested on mouse (Luc-4T1) and human (MDA-MB-231) breast cancer cell lines. The antiproliferative effect was evaluated through SRB screening and the MTT assay after 48 h of treatment at different concentrations. Interestingly, among the tested chalcone derivatives, chalcone analogues with a methoxy group were found to have significant anticancer activity and displayed gradient-dependent inhibition against breast cancer cell proliferation. The anticancer properties of these unique analogues were examined further by cytometric analysis of the cell cycle, quantitative PCR, and the caspases-Glo 3/7 assay. Chalcone methoxy derivatives showed the capability of cell cycle arrest and increased Bax/Bcl2 mRNA ratios as well as caspases 3/7 activity. The molecular docking analysis suggests that these chalcone methoxy derivatives may inhibit anti-apoptotic proteins, particularly cIAP1, BCL2, and EGFRK proteins. In conclusion, our findings confirm that chalcone methoxy derivatives could be considered to be potent drug candidates against breast cancer. [ABSTRACT FROM AUTHOR]

A series of bis-chalcones with alkyl linkers incorporating 3-(thiophen-2-yl)pyrazole 5–10 has been prepared by the condensation reaction of two moles of 3-(thiophen-2-yl)pyrazole-4-aldehyde 4 with one mole of bis- o- or p-(acetophenones) 3a-f. The synthesized compounds 5-10 have been fully characterized and tested as novel anti-cancer agents. The in vitro anticancer activities of the compounds 5-10 were evaluated against a panel of human cancer cell lines (A431, A549, and PC3), and a normal human skin fibroblast BJ1. Compound 10 was the most promising in the prepared series with IC50 (48.7 and 74.2 µg/mL) against epidermoid cancer cell line A431 and the lung adenocarcinoma cell line A549, respectively, compared to the reference drug doxorubicin (IC50, 28.3 and 27.9 µg/mL, respectively). The target compound 10 was investigated theoretically using molecular docking study to different domain sets (1dls, 2c6o, 2w3t, 4kmn, and 4wt2) and they illustrated different modes of action with different binding energies. [ABSTRACT FROM AUTHOR]

A series of fluorinated chalcones (3a-f) was synthesized and confirmed by several spectral tools. The cytotoxic effect of this series was tested against a panel of different cancer cell lines (MCF7, A549, HCT116, and PC3). MTT assay revealed that chalcone 3f has the potent cytotoxic activity against all tested cancer cell lines except A549 cells. Chalcone 3f showed the least cytotoxic activity against the normal epithelial cell line RPE-1 and the lowest IC50 at 10.96 µM relative to the IC50 of doxorubicin at 12.8 µM against the human breast cancer cell line MCF7. Molecular docking studies showed a good interaction of chalcone 3f with the active site of histone demethylase (PLU-1/JARID1B) and Carboxy-terminal binding protein1 (CtBP1) proteins. Mechanistically, chalcone 3f induced cell cycle arrest at G2/M phase and apoptosis assessed by flow cytometry, as well as DNA fragmentation in MCF7 cells. Chalcone 3f upregulated mRNA expression levels of the apoptotic genes BAX, p53, and Caspase-7, Caspase-8, and Caspase-9, whereas mRNA expression levels of the antiapoptotic gene Bcl2, metastasis-related gene matrix metalloproteinase 1 (MMP1), and the autophagic markers ATG5 and LC3B were downregulated as quantified by qPCR. This study shows a cytotoxic effect of chalcone 3f against cancer cells and emerges as a promising therapeutic drug against breast cancer. [ABSTRACT FROM AUTHOR]

AbstractSix substituted α-cyano-indolylchalcones have been prepared and their structures were verified by various spectral analysis tools. Compared with the standard drug 5-Fluorouracil) 5-FU(, the anticancer activity against prostate cancer (PC3) and breast cancer cell line (MCF7) was determined using the cytotoxic MTT assay. Also, the cytotoxic effect against normal melanocytes (HFB4) was studied to detect the selectivity of the compounds. Among the series, compound 3e was the most active and selective one toward MCF7 (IC50= 0.18 µmole/mL, SI= 7.6). In silico studies were performed to demonstrate the inhibitory effect of compound 3e on EGFRK, CDK2, and MDM2 domains. Different molecular techniques were performed to know the efficacy of the novel 3e on apoptotic death of breast carcinoma cells. [ABSTRACT FROM AUTHOR]

An efficient and convenient route for the synthesis of novel bis dihydropyrano[3,2‐c]chromenes is reported. The synthetic pathway involves one‐pot, multicomponent reaction of bis‐aldehydes, malononitrile, and 4‐hydroxycoumarin in the presence of pyridine or acetic acid/sodium acetate. A stepwise approach for the synthesis of the target compounds was also investigated. The anticancer activity of the synthesized products against MCF7, HEPG2, and A549 cell lines was assessed. Attempts to detect the molecular action of 6g, docking simulation was done using DHFR PDB:ID (1DLS). The study revealed that compound 6g was strongly fit into the active sites of the target protein through six bindings, and hence, it was considered as promising inhibitor for cancer proliferation. [ABSTRACT FROM AUTHOR]

An efficient route for the synthesis of novel bis(1,4-dihydropyrano[2,3- c ]pyrazole-5-carbonitrile) derivatives is reported. The synthetic pathway involves one pot, synthesis of bis-aldehydes, malononitrile, and pyrazolone in the presence of pyridine. The anticancer activity of the synthesized products against MCF7, HEPG2, and A549 cell lines was assessed. Docking studies were performed and indicated the best binding mode compared to the standard ligand sorafenib. [ABSTRACT FROM AUTHOR]

Objective: Coupling of ethyl 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)acetate 2 with diazotized anilines in ethanol in the presence of sodium acetate yielded 2-(2-arylhydrazono)-2-(6,7- dimethoxy-3,4-dihydroisoquinolin-1-yl)acetate (4a-f)., Methods: Treatment of 2 with α-bromoketones 6a-f in dry benzene at reflux gave the corresponding isoquinolinium bromides 7a-f. Refluxing of each of the salts 7a-f in dry benzene and in the presence of triethylamine yielded 2-arylpyrrolo-[2,1-a]isoquinoline structures 8a-f, that converted to ethyl (E)-8,9- dimethoxy-3-(phenyldiazen-yl)-2-(aryl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-1-carboxylate (9a-f) upon treatment with diazotized anilines 3 in ethanol in the presence of sodium acetate., Results and Conclusion: Cytotoxic assay was performed for in vitro antitumor screening against caucasian breast adenocarcinoma (MCF7), hepatocellular carcinoma (HepG2) and colorectal carcinoma (HCT-116) cell lines. The results were compared with the standard anticancer drug (doxorubicin). Molecular docking using MOE 2014.09 software was carried out for the most potent compound 4d, which showed the highest binding affinity towards the four tested proteins and thus initiated apoptosis of cancer cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)