Microwave-assisted synthesis, spectroscopic characterization, and biological evaluation of fused thieno[2,3-d]pyrimidines as potential anti-cancer agents targeting EGFRWT and EGFRT790M.

Epidermal growth factor receptor (EGFR) is a transmembrane protein tyrosine kinase that is usually overexpressed in many types of cancers. In the present study, an effort was done in synthesis of new 3,4-diaminothieno[2,3-b] thiophene-2,5-dicarbonitrile derivatives 2-8, assisted by a microwave device. Different spectroscopic instruments were used for their analysis and confirmed their chemical structures. The antimicrobial properties of the produced compounds were investigated and found to be promising. Next, they were tested for cytotoxicity against MCF-7, HepG-2, HCT-116, and A549 cell lines. Moreover, in vitro cytotoxicity evaluation against well-known standards, namely, gefitinib and erlotinib was achieved using MTT method. The obtained compounds (2-8) were found to be more effective against the two tested cancer cell lines than erlotinib. In MCF-7 and A549 cells, compound 3 was found to be 4.42 and 4.12 times more active than erlotinib, respectively. The activity of radical scavenging was inhibited by 78%. The most cytotoxic compounds were subsequently studied for their kinase inhibitory effect against EGFRWT and EGFRT790M using the HTRF assay. Compound 3 was shown to be the most powerful against both kinds of EGFR, with IC50 values of 0.28 and 5.02. Furthermore, compound 2 demonstrated the highest antioxidant activity as it has a radical scavenging activity of 78%. Compounds 2,6,7 and 8 revealed to be the most safe compounds, none hepatotoxic, none carcinogenic, none immunotoxic, none mutagenic and none cytotoxic.

Microwave-Assisted Synthesis, Biological Activity Evaluation, Molecular Docking, and ADMET Studies of Some Novel Pyrrolo [2,3-b] Pyrrole Derivatives.

Novel pyrrolo [2,3-b] pyrrole derivatives were synthesized and their hypolipidemic activity was assessed in hyperlipidemic rats. The chemical structures of the new derivatives were confirmed through spectral analysis. Compounds 5 and 6 were revealed to be the most effective hypolipidemic agents, with considerable hypocholesterolemic and hypotriglyceridemic effects. They appear to be promising candidates for creating new powerful derivatives with anti-atherosclerotic and hypolipidemic properties. As for antimicrobial activity, some of the tested compounds showed moderate activity against Pseudomonas aeruginosa: compound 2 revealed an MIC value of 50 µg/mL, compared to 25 µg/mL for ciprofloxacin. Compound 3 showed good antimicrobial activity against Staphylococcus aureus, comparable to ciprofloxacin, and roughly half the activity of ampicillin, according to MIC values. Compound 2 has an MIC approximately 25% of that of clotrimazole against Candida albicans. Compound 2 also showed the highest antioxidant activity with 59% inhibition of radical scavenging activity. Additionally, the cytotoxic activity of these new derivatives 1-7 was investigated and most of them showed good anticancer activity against the three tested cell lines.

Diffusion-weighted imaging versus dynamic contrast-enhanced MRI: a new horizon for characterisation of suspicious breast lesions.

AIM: To investigate the value of new diffusion-weighted imaging applications in the characterisation of suspicious breast lesions with emphasis on diffusion tensor imaging (DTI) and fibre tractography (FT). MATERIALS AND METHODS: The present prospective study included 40 female patients with suspicious breast lesions according to sono-mammography American College of Radiologists' classification. All patients underwent conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), DTI, and FT after meeting the inclusion criteria. Dynamic contrast-enhanced MRI was performed as the reference standard for radiological evaluation. The study was conducted between August 2018 and January 2019. The final diagnosis was confirmed histopathologically. RESULTS: Malignant lesions were diagnosed in 32/40 (80%) patients and 8/40 (20%) patients had benign lesions. Apparent diffusion coefficient (ADC) values of malignant lesions were statistically lower than that of benign lesions (p<0.001) using a cut-off value of 0.99±0.07×10-3 mm2/s. Fractional anisotropy (FA) values were lower in malignant lesions than in benign lesions with a cut-off value for malignancy of 0.19±0.05 and were statistically significant (p<0.005). The sensitivity, specificity, and accuracy of combined DTI and FT were similar to DCE MRI (p<0.001). CONCLUSION: DTI and FT are new applications of DWI. They show promising results for the evaluation of suspicious breast masses and can distinguish between benign and malignant breast lesions with statistical significance approaching contrast-enhanced MRI, which is considered the imaging reference standard for characterising breast lesions.

Design, synthesis and in vivo anti-inflammatory activities of 2,4-diaryl-5-4H-imidazolone derivatives.

A series of 2,4-diaryl-5(4H)-imidazolones were prepared and evaluated for their anti-inflammatory activities. Some selected 2,4-diaryl-5(4H)-imidazolones exhibited excellent anti-inflammatory activity in the carrageenan-induced rat paw edema model. Structure Activity Relationships within the series were studied. The substitution at the N-sulfonamide moiety by a small hydrophilic acetyl group resulted in compounds with superior in vivo anti-inflammatory properties. As expected from their COX-2 selectivity, most of the active compounds lacked gastrointestinal toxicity in vivo in rats after a 3-day treatment of 25 mg/kg/day.

Thieno[2,3-b]thiophene Derivatives as Potential EGFRWT and EGFRT790M Inhibitors with Antioxidant Activities: Microwave-Assisted Synthesis and Quantitative In Vitro and In Silico Studies.

Microwave-assisted synthesis and spectral analysis of certain novel derivatives of 3,4-diaminothieno[2,3-b]thiophene-2,5-dicarbonitrile 1-7 were carried out. Compounds 1-7 were examined for cytotoxicity against MCF-7 and A549 cell lines using the quantitative MTT method, and gefitinib and erlotinib were used as reference standards. Compounds 1-7 were shown to be more active than erlotinib against the two cell lines tested. Compound 2 outperformed regular erlotinib by 4.42- and 4.12-fold in MCF-7 and A549 cells, respectively. The most cytotoxic compounds were subsequently studied for their suppression of kinase activity using the homogeneous time-resolved fluorescence assay versus epidermal growth factor receptor (EGFRWT) and EGFR790M. With IC50 values of 0.28 ± 0.03 and 5.02 ± 0.19, compound 2 was demonstrated to be the most effective against both forms of EGFR. Furthermore, compound 2 also had the best antioxidant property, decreasing the radical scavenging activity by 78%. Molecular docking research, on the other hand, was carried out for the analyzed candidates (1-7) to study their mechanism of action as EGFR inhibitors. In silico absorption, distribution, metabolism, excretion, and toxicity tests were also performed to explain the physicochemical features of the examined derivatives.

Elemental investigation of some Egyptian vehicle motor alloys using neutron activation analysis.

Six samples of different Egyptian motor vehicle alloys have been investigated by neutron activation analysis to estimate the concentrations of their elemental constituents, which affect their quality. A single high resolution hyper-pure germanium HPGe gamma-ray detector and a multichannel analyzer are used to collect the gamma-ray spectra. A HPGe-HPGe coincidence spectrometer was also used to confirm the identity of certain peaks. Thirteen trace elements (Sc, Cr, Fe, Co, Zn, Sn, Sb, La, Sm, Eu, Hf, Pt and Au) were observed in the spectra and their concentrations were determined. A comparative study on the element concentrations for the six samples is given.

Synthesis and biological activity of dihydroimidazole and 3,4-dihydrobenzo[4,5]imidazo[1,2-a][1,3,5]triazins.

Reaction of 2-guanidinobenzimidazole with halogenated active methylenes and ketones gave dihydroimidazole and 3,4-dihydrobenzo[4,5]imidazo [1,2-a][1,3,5]triazin derivatives in very good yield. The anti-bacterial evaluation of the newly synthesized products against broad spectrum of bacteria was performed. Most of products showed high inhibitory effect. All compounds have been characterized based on IR, (1)H NMR, (13)C NMR and Mass spectra.