Synthesis of 1,2,4-triazolopyridazines,isoxazolofuropyridazines, and tetrazolopyridazines as antimicrobial agents

Through current and previous researches, it was found that the derivatives of pyridazine, isoxazole, tetrazole, quinazoline, hydrazinyl, and 1,2,4-triazole have many pharmacological activities. Thus, a series of novel furopyridazinones ( 7 ), isoxazolopyridazine ( 8 ), sub-benzylidene-furopyridazinones ( 9a-c ), isoxazolofuropyridazines ( 10a-c ), 3-chloro-(pyridin-4-ylmethylene)-dihydropyridazines ( 11 ), tetrazolopyridazines ( 12 ), pyridazinoquinazolinones ( 13 ), piperazinyl/morpholino-pyridazines ( 14a,b ), hydrazinyl-pyridazines ( 15 ), and 1,2,4-triazolo-pyridazines ( 16a,b ) in good yields (72%-90%) were synthesized from substituted ethyl 4-oxo-4-phenylbutanoate ( 2 ), 6-phenyl-4,5-dihydropyridazinone ( 3 ), and 6-phenyl-4-(pyridin-4-ylmethylene)-4,5-dihydropyridazinone ( 4 ) as beginning materials. All the chemical structures of the new compounds have been demonstrated by different spectroscopy analyses such as infrared, NMR, mass spectrum, and elemental analysis. Also, the activities of the newly prepared compounds were tested against many types of bacteria and fungi in vitro. Hence, 1,2,4-triazolopyridazines ( 16a,b ), isoxazolofuropyridazines ( 10a-c ), tetrazolopyridazines ( 12 ), Piperazinyl/morpholinyl-pyridazines ( 14a,b ) displayed the most efficient antimicrobial activities compared with the cefotaxime sodium and nystatin as standard drugs.     

Luminescence recognition of different organophosphorus pesticides by the luminescent Eu(III)–pyridine-2,6-dicarboxylic acid probe

Luminescence quenching of a novel long lived Eu(III)–pyridine-2,6-dicarboxylic acid probe of 1:2 stoichiometric ratio has been studied in 0.10 volume fraction ethanol–water mixture at pH 7.5 (HEPES buffer) in the presence of the organophosphorus pesticides chlorfenvinphos (P1), malathion (P2), azinphos (P3), and paraxon ethyl (P4). The luminescence intensity of Eu(III)–(PDCA)₂ probe decreases as the concentration of the pesticide increases. It was observed that the quenching due to P3 and P4 proceeds via both diffusional and static quenching processes. Direct methods for the determination of the pesticides under investigation have been developed using the luminescence quenching of Eu(III)–pyridine-2,6-dicarboxylic acid probe in solution. The linear range for determination of the selected pesticides is 1.0–35.0 μM. The detection limits were 0.24–0.55 μM for P3, P4, and P1 and 2.5 μM for P2, respectively. The binding constants (K), and thermodynamic parameters of the OPs with Eu(III)–(PDCA)₂ were evaluated. Positive and negative values of entropy (ΔS) and enthalpy (ΔH) changes for Eu(III)–(PDCA)₂–P1 ternary complex were calculated. As the waters in this study do not contain the above mentioned OPs over the limit detectable by the method, a recovery study was carried out after the addition of the adequate amounts of the organophosphorus pesticides under investigation.     

Synthesis,molecular docking,antimicrobial, antiquorum-sensing and antiproliferative activities of new series of pyrazolo[3,4-b]pyridine analogs

New series of pyrazolo[3,4-b]pyridines were prepared and evaluated for antimicrobial activity toward six selected microorganisms. Compounds 2a, 3b, 3d and 3e exhibited good activity toward B. cereus. On the other hand, 2a and 3b evinced interesting activity over C. albicans, whereas 2a, 3b and 3e displayed promising activity over A. fumigatus. Antiquorum-sensing effectiveness of the new members over C. violaceum was also assessed, where compounds 2a and 3b exhibited higher activity than that of the reference compound, indole. In vitro antiproliferative assessment toward HepG2, HCT-116 and MCF-7 cancer cells evidenced that 2f has notable effectiveness on all examined cell lines, whereas 3a–c were active but to a lower extent. In vivo antitumor activity of 2f and 3a–c against EAC cells was also esteemed, where 2f and 3c showed considerable activity comparable to that of doxorubicin. Cytotoxicity screening over WI38 and WISH normal cells evinced that 2f and 3a–c are less cytotoxic than doxorubicin. Compounds 2a, 2f, 3a–c and 3e were evaluated for DNA-binding affinity and topoisomerase IIβ inhibitory activity. Analogs 2a, 2f, 3a and 3b illustrated strong DNA-binding affinity, whereas 2a, 2f and 3a exhibited interesting topoisomerase IIβ inhibitory activity. Compounds 2a and 2f were docked into topoisomerase IIβ, where 2f showed preferential binding to topoisomerase IIβ. Computational studies articulated that the new members are in compliance with Veber's standards and Lipinski’s rule.     

Electronic Absorption Spectra of Some 2-Thiouracil Derivatives

Abstract

The electronic absorption spectra of 2-thiouracil and some of its derivatives were investigated using polar and nonpolar solvents. The present analysis is facilitated via computer deconvolution of the observed spectra and molecular orbital (MO) computations. Comparison between the experimentally observed and theoretically computed spectra in addition to a quantitative assignment of all transitions observed were undertaken. The computed dipole moments are used to indicate the polarity of the excited state and hence predict its solvent dependence. The spectra are, in general, very well predicted and assigned using INDO/S computational results. The spectrum of the trifluoro derivative is much more complicated and the corresponding states show much more solvent dependence than those observed for other thiouracil studied.     

Synthesis of Some New Thieno[2,3-b]pyridines,Pyrimidino[4′,5′:4,5]thieno[2,3-b]-pyridines,and 2,3-Dihydro-1,3,4-thiadiazoles

Thieno[2,3-b]pyridines were synthesized from 6-benzofuran-2-yl-4-phenyl-2-sulfanylpyridine-3-carbonitrile and each of chloro acetone, ethyl chloroacetate, ω -bromoacetophenone, and chloroacetonitrile. These compounds were conveniently converted into novel pyrido[4′,5′:4,5]thieno[3,2-d]pyrimidines. Also, 2,3-dihydro-1,3,4-thiadiazole was synthesized from hydrazonoyl halides and 2-benzofuran-2-yl-3-(phenylamino)-3-thioxopropanenitrile. The structures of the products have been elucidated by elemental analyses, spectral data studies, and alternative syntheses whenever possible. The newly synthesized compounds were tested towards microorganisms.     

Synthesis of Some New Polyfused Thienothiophenes Part 4: Synthesis of Thienopyrimidine,Thienotriazine, Thienoimidazotriazine,Thienotriazolotriazine, and Thienotetrazolotriazine Derivatives

3,4-Diamino-2,5-dicarboxamidothieno(2,3-b)thiophene 1 was allowed to react with CS 2 , carbonyl compounds, ethyl chloroformate, S,S-acetals, and oxallyl chloride to give thienopyrimidines 2-6 and thieno-1,4-diazepine 7 . Treatment of compound 1 with nitrous acid afforded compound 8 , which converted into the corresponding chloro derivative 9 by using PCl 5 . Compound 9 was reacted with amino reagents to afford the corresponding thienoimidazotriazines 10 and 11 , thienotriazolotriazines 12 and 13 and 4-hydrazinothienotriazine 14 . Treatment of compound 14 with aldehydes, triethyl orthoformate, CS 2 , nitrous acid and ylidenemalononitriles, afforded thienotriazolotriazine 16-18 , thienotetrazolotriazine 19 , and 4-pyrazolyl-thienotriazine 20-22 derivatives respectively.     

Supramolecular Self Assembly of [Cu(CN)4]3− Ions with Cationic {Ph3Sn+} Units in the Presence of Neutral Bidentate Ligands

The supramolecular interplay of the Ph ₃ Sn⁺ unit and the [Cu(CN) ₄ ]^3? ion with either 4,4′-bipyridine (bpy), trans-1,2-bis(4-pyridyl)ethene (tbpe), 1,2-bis(4-pyridyl)ethane (bpe), pyrazine (pyz), or methylpyrazine (mepyz) as bidentate ligands in presence of H ₂ O has been investigated for the first time. The products obtained have the general formula [(Ph ₃ Sn) ₃ Cu(CN)₄·L·XH₂O], where L is a bidentate ligand and X = 0–2. H ₂ O molecules are usually coordinated to tin atoms and are involved in two significant O─H─N hydrogen bonds, wherein the nitrogen atoms belong either to the bidentate ligand or the M-coordinated cyanide ligands. The structures of these supramolecular coordination polymers were investigated by elemental analysis, X-ray powder diffraction, and IR, mass, and NMR spectra.     

Homopolymerization of Maleic Anhydride

It is well known that molecular oxygen inhibits the homopolymerization of vinyl-type monomers [1]. During several attempts in this laboratory to homopolymerize vinyl acetate in benzene, no polymer was formed over a period of one week, even though the initiator was varied as to type and concentration.     

Physicochemical Characterization of Acidiphilium sp. Biofilms

The biofilm formation of a strain of the extremophile bacterium Acidiphilium sp., capable of donating electrons directly to electrodes, was studied by different surface characterization techniques. We develop a method that allows the simultaneous study of bacterial biofilms by means of fluorescence microscopy and atomic force microscopy (AFM), in which transparent graphitic flakes deposited on a glass substrate are used as a support for the biofilm. The majority of the cells present on the surface were viable, and the growth of the biofilms over time showed a critical increase of the extracellular polymeric substances (EPS) as well as the formation of nanosized particles inside the biofilm. Also, the presence of Fe in Acidiphilium biofilms was determined by X‐ray photoelectron spectroscopy (XPS), whereas surface‐enhanced infrared absorption spectroscopy indicated the presence of redox‐active proteins.     

Inverse gas chromatographic characterization of Porapak Q as an extractant of pollutants from aqueous media

The surface of Porapak Q was characterized by inverse gas chromatography (IGC) carried out by the determination of dispersive and specific adsorption components of Porapak Q surface, calculating γ_s^d and -ΔH _a^s parameters, respectively. An interpretation was given based on the chemical structure of Porapak Q. The obtained results were confirmed through the surface Lewis acidity and basicity constants, K _a and K _b, respectively, correlating well with the determined thermodynamic parameters.