Synthesis of some new Thienopyrimidine with Benzoxazine, Quinazoline and Azole Moieties

Reaction of thienopyrimidinoyl chloride 3 with  2-aminocyclohexanothiophene-3-carboxamide 4 yielded thienopyrimidine derivative 5 that undergoes cyclodehydration to afford thienopyrimidine 6. The synthesis of benzamidazole 8 and benzoxazole 10 derivatives was achieved by condensation of thienopyrimidinoyl chloride 3 and o-phenylenediamine / o-aminophenol followed by cyclization. Reaction of 4-thio-6-methyl-2-(p-methoxyphenyl)-5-acetylpyrimidine 1 and N(o-carboxyphenyl) chloroacetamide11 yielded pyrimidine derivative 12 that cyclized to benzoxazine 13. Compound 13 was transformed to quinazoline derivatives 14a-c and 16. Reaction of 13 with semicarbazide yielded triazoloquinazoline 18

Heterociklički derivati 3-(4-bromfenil) azo-5-fenil-2(3H)-furanona: Djelovanje na virus ptičje gripe (H5N1)

3-[2-(4-Bromphenyl)hydrazono]-5-phenyl-furan-2(3H)-one (1) was used for preparation of some novel pyrazole, pyridazinone, oxadiazole, triazole, thiazolidine and thioxo-pyrimidine derivatives. Some of the prepared products were tested for anti-avian influenza virus activity and revealed promising antiviral activity against H5N1 virus [A/Chicken/Egypt/1/20 % (H5N1)] by determination of both EC50 and LD50 and confirmed by plaque reduction assay on MDCK cells. Compounds 3-[2-(4-bromophenyl)hydrazono]-5-phenylfuran-2(3H)-one 1, 1-(4-bromophenyl)-N-hydroxy-5-phenyl-1H-pyrazole-3-carboxamide 5 and 1-(4-bromophenyl)-N-{2,3-dihydro-4-hydroxy-3-phenyl-6-oxo-2-thioxopyrimidin-1(6H)-yl}-5-phenyl-1H-pyrazole-3-carboxamide (12a) showed the highest effects. Detailed synthesis, spectroscopic data, and antiviral activity of the synthesized compounds are reported.3-[2-(4-Bromfenil)hidrazono]-5-fenil-furan-2(3H)-on (1) upotrjebljen je za pripravu novih derivata pirazola, piridazinona, oksadiazola, triazola, tiazolidina i tioksopirimidina. Neki od sintetiziranih spojeva imaju virustatski učinak na virus ptičje gripe H5N1. Farmakološki aktivnim spojevima određeni su EC50 i LD50 i dobiven je pozitivni test redukcije plaka na MDCK staničnoj liniji. Najjači učinak pokazali su 3-[2-(4-bromfenil)hidrazono]-5-fenilfuran-2(3H)-on (1), 1-(4-bromfenil)-N-hidroksi-5-fenil-1H-pirazol-3-karboksamid (5) i 1-(4-bromfenil)-N-{2,3-dihidro-4-hidroksi-3-fenil-6-okso-2-tioksopirimidin-1(6H)-il}-5-fenil-1H-pirazol-3-karboksamid (12a). Detaljno su opisani priprava, spektroskopski podaci i antivirusno djelovanje sintetiziranih spojeva

Antimikrobno djelovanje nekih glukopiranozil-pirimidin karbonitrila i fuzioniranih pirimidinskih sustava

3-Amino-5-(4-chlorophenylamino)-4-cyanofuran-2-carboxamide (2) was used as the key molecule for preparation of various furo- pyrimidines 3-9 and formation of spiro-cycloalkane furopyrimidines 10, 11. Also, poly fused heterocyclic compounds 13-17 were prepared from compound 2. The synthesized compounds were screened for their antimicrobial activity.3-Amino-5-(4-klorfenilamino)-4-cijanofuran-2-karboksamid (2) upotrebljen je kao ključni spoj za pripravu različitih furo-pirimidina 3-9 i spiro-cikloalkane furopirimidina 10 i 11. Fuzionirani heterociklički spojevi 13-17 pripravljeni su također polazeći iz spoja 2. Sintetizirani spojevi ispitani su na antimikrobno djelovanje

Nanoparticles of a pyrazolo-pyridazine derivative as potential EGFR and CDK-2 inhibitors: design, structure determination, anticancer evaluation and in silico studies

The strategic planning of this study is based upon using the nanoformulation method to prepare nanoparticles 4-SLNs and 4-LPHNPs of the previously prepared 4,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-amine (4) after confirming its structure with single crystal X-ray analysis. These nanoparticles exhibited promising cytotoxic activity against HepG-2, HCT-116 and MCF-7 cancer cell lines in comparison with the reference doxorubicin and the original derivative 4. Moreover, their inhibitory assessment against EGFR and CDK-2/cyclin A2 displayed improved and more favorable impact than the parent 4 and the references. Detection of their influence upon cancer biomarkers revealed upregulation of Bax, p53 and caspase-3 levels and downregulation of Bcl-2 levels. The docking simulation demonstrated that the presence of the pyrazolo[3,4-c]pyridazin-3-amine scaffold is amenable to enclosure and binding well within EGFR and CDK-2 receptors through different hydrophilic interactions. The pharmacokinetic and physicochemical properties of target 4 were also assessed with ADME investigation, and the outcome indicated good drug-like characteristics

Synthesis of some new pyridine-2,6-carboxamidederived Schiff bases as potential antimicrobial agents

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Synthesis of Some Novel Heterocyclic and Schiff Base Derivatives as Antimicrobial Agents

Treatment of 2,3-diaryloxirane-2,3-dicarbonitriles 1a–c with different nitrogen nucleophiles, e.g., hydrazine, methyl hydrazine, phenyl hydrazine, hydroxylamine, thiosemicarbazide, and/or 2-amino-5-phenyl-1,3,4-thiadiazole, afforded pyrazole, isoxazole, pyrrolotriazine, imidazolothiadiazole derivatives 2–5, respectively. Reacting pyrazoles 2a–c with aromatic aldehydes and/or methyl glycinate produced Schiff’s bases 7a–d and pyrazolo[3,4-b]-pyrazinone derivative 8, respectively. Treating 7 with ammonium acetate and/or hydrazine hydrate, furnished the imidazolopyrazole and pyrazolotriazine derivatives 9 and 10, respectively. Reaction of 8 with chloroacetic acid and/or diethyl malonate gave tricyclic compound 11 and triketone 12, respectively. On the other hand, compound 1 was reacted with active methylene precursors, e.g., acetylacetone and/or cyclopentanone producing adducts 14a,b which upon fusion with ammonium acetate furnished the 3-pyridone derivatives 15a,b, respectively. Some of newly synthesized compounds were screened for activity against bacterial and fungal strains and most of the newly synthesized compounds showed high antimicrobial activities. The structures of the new compounds were elucidated using IR, 1H-NMR, 13C-NMR and mass spectroscopy

All-Solid-State Calcium Sensors Modified with Polypyrrol (PPY) and Graphene Oxide (GO) as Solid-Contact Ion-to-Electron Transducers

Reliable, cost-effective, and robust screen-printed sensors were constructed and presented for Ca2+ ions determination. The sensors were based on the use of bilirubin (1,3,6,7-tetramethyl-4,5- dicarboxyethy-2,8-divinyl-(b-13)-dihydrobilenone) as a recognition sensory material in plasticized poly (vinyl chloride) (PVC) membranes. Polypyrrol (PPY) and graphene oxide (GO) were used as ion-to-electron transducers, where the effects of anionic excluder, pH, and selectivity were investigated. In a 50 mM tris buffer solution of pH 5, the electrodes offered a potential response for Ca2+ ions with a near-Nernstian slopes of 38.1 ± 0.4 (r2 = 0.996) and 31.1 ± 0.6 (r2 = 0.999), detection limits 3.8 × 10−6 (0.152 μg/mL) and 2.3 × 10−7 M (8.0 ng/mL), and linear concentration ranges of 7.0 × 10−6–1.0 × 10−2 (400–0.28 μg/mL) and 7.0 × 10−7–1.0 × 10−2 M (400–0.028 μg/mL) for sensors based on PPY and GO, respectively. Both sensors revealed stable potentiometric responses with excellent reproducibility and enhanced selectivity over a number of most common metal ions, such as Na+, K+, Li+, NH4+, Fe2+, Mg2+, and Ba2+. Impedance spectroscopy and chronopotentiometric techniques were used for evaluating the potential drift and the interfacial sensor capacitance. The proposed sensors offered the advantages of simple design, ability of miniaturization, good potential stability, and cost-effectiveness. The developed electrodes were applied successfully to Ca2+ ion assessment in different pharmaceutical products, baby-food formulations, and human blood samples. The results obtained were compared with data obtained by atomic absorption spectrometry (AAS)

Behaviour of Thienopyrimidinoylisothiocyanate towards Nitrogen and Carbon Nucleophiles

Addition of aryl amine and urea derivatives to isothiocyanate 2 yielded thiourea derivatives 3a-c and triazine derivatives 4a,b respectively. Cycloaddition of isothiocyanate 2 and malononitrile, Schiff base and / or enaminone 8 afforded oxazine 5, oxadiazine 7 and / or pyrimidine 9 derivatives respectively

Cytotoxic Effects of Newly Synthesized Heterocyclic Candidates Containing Nicotinonitrile and Pyrazole Moieties on Hepatocellular and Cervical Carcinomas

In this study, a series of newly synthesized substituted pyridine 9, 11−18, naphthpyridine derivative 10 and substituted pyrazolopyridines 19−23 by using cycnopyridone 8 as a starting material. Some of the synthesized candidates are evaluated as anticancer agents against different cancer cell lines. In vitro cytotoxic activities against hepatocellular and cervical carcinoma cell lines were evaluated using standard MTT assay. Different synthesized compounds exhibited potential in vitro cytotoxic activities against both HepG2 and HeLa cell lines. Furthermore, compared to standard positive control drugs, compounds 13 and 19 showed the most potent cytotoxic effect with IC50 values of 8.78 ± 0.7, 5.16 ± 0.4 μg/mL, and 15.32 ± 1.2 and 4.26 ± 0.3 μg/mL for HepG2 and HeLa cells, respectively