Ahmed F. Darweesh

A convenient synthesis of pyrazole-substituted heterocycles

(E)-1-(5-Methyl-1-phenylpyrazol-4-yl)-3-(N,N-dimethylamino)-2-propen-1-one reacts with hydrazine, hydroxylamine, guanidine and aminopyrazole derivatives to afford the corresponding 3,4′-bipyrazole, pyrazolylisoxazole, pyrazolylpyrimidine and pyrazolo[1,5-a]pyrimidine derivatives, respectively. It reacts also with benzoquinone, naphthoquinone and N-benzoylglycine to give the corresponding benzofuran and pyrazolylpyranone derivatives, respectively.

Synthesis, characterization and antitumor activity of novel tetrapodal 1,4-dihydropyridines: p53 induction, cell cycle arrest and low damage effect on normal cells induced by genotoxic factor H2O2

Synthesis of novel tetrakis(2,6-dimethyl-4-phenyl-1,4-dihydropyridinyl)methanes 5a–d by acid-catalyzed condensation of the tetrakis-aldehydes 6a–d with eight equivalents of 3-aminobut-2-enenitrile 2 is reported. The structures of 5a–d are confirmed by different spectral tools. In vitro, cytotoxic screening assay for novel tetrapodal 1,4-dihydropyridines (5a–d) was performed on five different human cell lines (HCT116, A549, MCF7, PC3, and HEPG2). The compounds showed higher cytotoxic activity against (A549, HCT116, and MCF7) cell lines. The loss of the cytotoxic activity was observed in the case of PC3 and HEPG2 cell lines. Compound 5b showed the highest cytotoxic activity against the three lines (A549, HCT116, and MCF7). In an attempt to know the mechanism followed by the compounds to inhibit cell proliferation, compound 5b was chosen for molecular studies. Compound 5b induced apoptotic inhibition of the proliferation of human colon adenocarcinoma HCT116 cells through induction of the tumor suppressor protein p53, BAX, and through the inhibition of anti-apoptotic proteins by decreasing BCL2 gene expression using real-time PCR. Regarding cell cycle analysis, compound 5b induced G1 arrest against the three lines (MCF7, HCT116, and A549). Compound 5b has been found to reduce apoptosis of human normal melanocytes HFB4 and normal fibroblasts BHK that has been treated with genotoxic factor H2O2. Moreover, compound 5b has a potent protective effect against DNA damage, as indicated by the in vitro studying of different concentrations of 5b against two different types of healthy DNA (calf-thymus DNA and pBR322 DNA).

Molecular docking simulation and anticancer assessment on human breast carcinoma cell line using novel bis(1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile) and bis(1,4-dihydropyrazolo[4',3':5,6]pyrano[2,3-b]pyridine-6-carbonitrile) derivatives.

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.

Regioselective synthesis and theoretical studies of novel bis(tetrahydro[1,2,4]triazolo[5,1- b ]quinazolin-8(4 H )-ones) catalyzed by ZnO nanoparticles

A novel series of bis(tetrahydro[1,2,4]triazolo[5,1-b]quinazolin-8(4H)-ones) were prepared in a regioselective manner via a three component reaction of bis-aldehydes with 5-amino-1,2,4-triazole and dimedone under microwave irradiation as well as under conventional heating. The reactions were carried out in the absence as well as in the presence of ZnO nanoparticles as a heterogeneous catalyst. Best results were achieved when these reactions were carried out under MW heating. The presence of ZnO nanoparticles was found to improve the yields of the reactions but did not change the regioselectivity the products. The reaction mechanism and the unambiguous structural elucidation of the expected regioisomers were studied using DFT calculations as well as 2D-HMBC spectroscopy.Graphical abstract

2-Mercapto-4,6-disubstituted nicotinonitriles: versatile precursors for novel mono- and bis[thienopyridines]

ABSTRACT A series of novel thieno[2,3-b]pyridines were prepared from the reaction of the appropriate bromoacetylbenzofurans or bromoacetylbenzothiazole with the corresponding pyridinethione derivatives in ethanolic sodium ethoxide at reflux. Moreover, new bis(thieno[2,3-b]pyridine) derivatives have also been synthesized by the reaction of the appropriate bis-bromoacetyl derivatives with the corresponding pyridinethiones in the presence of sodium ethoxide. Attempts to synthesize the target bis(thieno[2,3-b]pyridine) derivatives by bis-alkylation of the corresponding (thieno[2,3-b]pyridin-2-yl)(hydroxyphenyl)methanone with the appropriate dihaloalkanes using a mild base were unsuccessful. GRAPHICAL ABSTRACT

Efficient, microwave-mediated synthesis of benzothiazole- and benzimidazole-based heterocycles

Abstract1-(Benzothiazol-2-yl)-3-(N,N-dimethylamino)-2-(phenylsulfonyl)prop-2-en-1-one (3) and 1-(1-methylbenzimidazol-2-yl)-3-(N,N-dimethylamino)-2-(phenylsulfonyl)prop-2-en-1-one (4) were obtained from the reaction of 1-(benzothiazothiazol-2-yl)-2-phenylsulfonyl-1-ethanone (1) and 1-(1-methyl-1H-benzimidazol-2-yl)-2-(phenylsulfonyl)-1-ethanone (2) with N,N-dimethylformamide dimethyl acetal, respectively. The enaminosulfones 3 and 4 were used as versatile building blocks for the synthesis of novel pyrazolo[1,5-a]pyrimidine and [1,2,4]-triazolo[1,5-a]pyramidine derivatives via their reactions with the appropriate aminopyrazoles and aminotriazole under both microwave and thermal reaction conditions. They have been also utilized as reactive synthons for the construction of novel pyrimido[1,2-a]benzimidazole, pyrido[1,2-a]benzimidazole, pyrimidine, isoxazole and pyrazole heterocycles pendent to benzothiazole and benzimidazole ring systems.

Novel bis(benzothiazole-oxime)-based Pd(II)-complex: synthesis, characterization, quantum chemical calculations, and catalytic significance in Suzuki–Miyaura and Heck–Mizoroki cross coupling reactions

In the present work, a novel binuclear benzothiazole-oxime Pd(II) complex was synthesized, characterized (elemental analysis, infrared spectroscopy, thermogravimetric analysis, ultraviolet–visible spectroscopy, nuclear magnetic resonance, and conductance measurements), and explored for its catalytic activity in Suzuki–Miyaura and Heck–Mizoroki cross-coupling reactions of different aryl- and heteroaryl halides with arylboronic acids and styrene, respectively, using the microwave irradiation conditions. The electronic arrangement, type of hybridization, and nature of bonding in the Pd-complex were investigated by natural bond orbital analysis. Time-dependent density functional theory calculations were carried out to understand the electronic transitions in the related experimental observations.Graphical abstract