Abdel-Sattar S. Hamad Elgazwy

A convenient synthesis and molecular modeling study of novel purine and pyrimidine derivatives as CDK2/cyclin A3 inhibitors

A series of novel purine and pyrimidine derivatives were prepared and biologically evaluated for their in vitro anti-CDK2/cyclin A3 and antitumor activities in Ehrlich ascites carcinoma (EAC) cell based assay. The novel purine derivatives 13a,b demonstrated potent inhibitor activities with IC(50) values of 14±9 and 13±9 μM, respectively. Additionally, compound 15a showed the highest potency (IC(50)=10±6 μM) in EAC cell based assay. Molecular modeling study, including fitting to a 3D-pharmacophore model and their docking into cyclin dependant kinase2 (CDK2) active site showed high fit values and docking scores.

A convenient synthesis and molecular modeling study of novel pyrazolo[3,4-d]pyrimidine and pyrazole derivatives as anti-tumor agents

Abstract An efficient method to obtain ethyl 5-amino-1-tosyl-1H-pyrazole-4-carboxylate (3) was outlined using condensation reactions of 4-methylbenzenesulfonylhydrazide with (E)-ethyl 2-cyano-3-ethoxyacrylate. The cyclocondensation reaction of this substrate and its hydrazide derivative with urea, thiourea, formamide, formic acid, d-glucose, o-phenylenediamine, 4-dimethylaminobenzaldehyde, anthracene-9-carbaldehyde, thioglycolic acid and carbon disulphide then with hydrazine hydrate analogues furnished a series of pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4-d]oxazin-4-one, pyrazole-4-glucoside, 4-benzo[d]imidazole, 1,3-thiazolidinone, 1,3,4-oxadiazol-2(3H)-thione and 1,2,4-triazol-5(4H)-thione derivatives respectively. The structure of the compound 3 was supported by X-Ray crystallographic data. Orally administrated, one of each of the series of pyrazoles showed significant effects in mouse tumor model cancer cell lines (EAC) and two human cancer cell lines of Colon cancer (HCT-29) and Breast cancer (MCF-7) with docking studies.

Synthesis, Biological Evaluation of Some 2,3-dihydropyrazoles and Thiazoles as Anti-inflammatory and Antibacterial Agents

The present article describes the synthesis of two novel series of 5-(benzofuran-2-yl)-3-(4-(piperidin-1-yl)phenyl)- 2,3-dihydropyrazole-1-carbothioamide 6 and 1-(4-(3-(benzofuran-2-yl)-2-(4-arylthiazol-2-yl)-2,5-dihydro-1H-pyrazol- 5-yl)phenyl)piperidine 8a-d. All the newly synthesized target compounds (3, 4, 5, 6 and 8a-d) were screened for their in vivo anti-inflammatory (AI) activity using carrageenan-induced rat paw edema assay and in vitro antibacterial activity against two Gram-positive and two Gram-negative bacteria. All eight compounds (3, 4, 5, 6, and 8a-d) showed consistently excellent AI activity (≥ 70% inhibition), at 3 and 4 h after the carrageenan injection, comparable to that of standard drug indomethacin (78%) whereas the remaining twelve compounds have shown significant activity with 57–75% inhibition after 3 h and 56–63% inhibition after 4 h. All the tested compounds showed moderate antibacterial properties.

Molecular modeling study bioactive natural product of khellin analogues as a novel potential pharmacophore of EGFR inhibitors

Khelline is naturally occurring furochromone exhibited significant Epidermal Growth Factor Receptor (EGFR) inhibitory activity. The newly synthesized compounds 2–5 displayed the most potent EGFR inhibitory activity on MCF-7 and HeLa. In vitro study against 59 different human tumour cell lines derived from nine cancer type in NCI (USA), which was presented and documented. Molecular docking simulation was performed to position compounds 1–5 into the EGFR active site to determine the probable binding mode.

Ethyl 5-amino-1-[(4-methyl­phen­yl)sulfon­yl]-1H-pyrazole-4-carboxyl­ate

In the title molecule, C13H15N3O4S, the benzene and pyrazole rings are inclined to each other at 77.48 (3)°. Two amino H atoms are involved in bifurcated hydrogen bonds, viz. intramolecular N—H⋯O and intermolecular N—H⋯O(N). The intermolecular hydrogen bonds link the molecules related by translation in [100] into chains. A short distance of 3.680 (3) Å between the centroids of benzene and pyrazole rings from neighbouring molecules shows the presence of π–π interactions, which link the hydrogen-bonded chains into layers parallel to the ab plane.

Three-dimensional quantitative structure activity relationship (QSAR) of cytotoxic active 3,5-diaryl-4,5-dihydropyrazole analogs: a comparative molecular field analysis (CoMFA) revisited study.

In vitro antitumor evaluation of the synthesized 46 compounds of 3,5-diaryl-4,5-dihydropyrazoles against EAC cell lines and 3D QSAR study using pharmacophore and Comparative Molecular Field Analysis (CoMFA) methods were described. CoMFA derived QSAR model shows a good conventional squared correlation coefficient r2 and cross validated correlation coefficient r2cv 0.896 and 0.568 respectively. In this analysis steric and electrostatic field contribute to the QSAR equation by 70% and 30% respectively, suggesting that variation in biological activity of the compounds is dominated by differences in steric (van der Waals) interactions. To visualize the CoMFA steric and electrostatic field from partial least squares (PLS) analysis, contour maps are plotted as percentage contribution to the QSAR equation and are associated with the differences in biological activity.BackgroundPyrazole derivatives exhibit a wide range of biological properties including promising antitumor activity. Furthermore, Aldol condensation assisted organic synthesis has delivered rapid routes to N-containing heterocycles, including pyrazoles. Combining these features, the use of chalconisation-assisted processes will provide rapid access to a targeted dihydropyrazoles library bearing a hydrazino 3D QSAR study using pharmacophore and Comparative Molecular Field Analysis (CoMFA) methods were described for evaluation of antioxidant properties.ResultsChalcones promoted 1 of the 2 steps in a rapid, convergent synthesis of a small library of hydrazinyl pyrazole derivatives, all of which exhibited significant antitumor activity against Ehrlich Ascites Carcinoma (EAC) human tumor cell line comparable to that of the natural anticancer doxorubicin, as a reference standard during this study. In order to understand the observed pharmacological properties, quantitative structure-activity relationship (3D QSAR) study was initiated.ConclusionsChalcones heating provides a rapid and expedient route to a series of pyrazoles to investigate their chracterization scavenging properties. Given their favorable properties, in comparison with known anticancer, these pyrazole derivatives are promising leads for further development and optimization.

A second polymorph of (Z)-3-amino-4-(2-phenyl­hydrazinyl­idene)-1H-pyrazol-5(4H)-one

The molecule of the title compound, C9H9N5O, is approximately planar (the r.m.s. deviation of all non-H atoms is 0.08 Å). The amine substituent is pyramidal at the N atom. An intramolecular N—Hhydrazine⋯O=C hydrogen bond is present. In the crystal, molecules are connected via N—H⋯N and N—H⋯O hydrogen bonds, forming infinite layers parallel to (010). This polymorph is triclinic, space group P-1, whereas the previously reported form was monoclinic, space group P21/c [Elgemeie et al. (2013 ▶). Acta Cryst. E69, o187], with stepped layers and a significantly lower density.

Synthesis of Novel Palladacycles Inhibitors of the Cathepsin B Activity and Antitumoral Agents

The reaction of 2-bromo-3,4,5-trimethoxybenzaldehyde 1 with Pd(dba) 2 ; dba=dibenzylideneacetone) in the presence of a stoichiometric amount of nitrogen donor ligands, such as N,N,N’,N’ -tetramethyl-ethane-1,2-diamine (TMEDA), 2,2’-bipyridine (bpy) 4,4’-dimethyl-2,2’-bipyridine (dmbpy) and an 1,10-phenanthroline (Phen), should be added to with equimolar ratio in degassed acetoneunder nitrogen to give mononuclear σ-aryl palladium (II) complexes cis-[2- Pd{C 6 H(CHO)-6-(OMe) 3 -3,4,5}BrL 2 ] 3a-d, where L 2 =TMEDA (3a); L 2 =bpy (3b); L 2 =dmbpy (3c); L 2 =Phen (3d) in good yields 48-65%. The reaction of the synthesized five-membered C,N -palladacycle cis-[2-Pd{C 6 H(CHO)-6-(OMe) 3 -3,4,5} BrL 2 ] 3a-d, where L 2 =TMEDA (3a); L=bpy (3b); L 2 =dmbpy (3c); L 2 =Phen (3d), with an1-naphthylisocyanates (C 10 H 7 - NCO) and an 1-naphthylisothiocyanates (C 10 H 7 -NCS), leads to the formation of novel palladacycle 4a-d and 5a-d, which was characterized in solution by 1 H NMR spectroscopy. The solid products were characterized by satisfactory elemental analysis and spectra studies. All the resulting complexes 3a-d, 4a-d and 5a-d were tested in vitro against a number of cell lines. For example, it inhibited K562 leukaemia cells with an IC 50 value in the range of (3.00 -4.3) μM (1 h exposure) and displayed cathepsin B inhibitory action with an IC 50 value in the range of (0.045-0.055 μM)

Thermo-Chemical Study on Complexes of Nickel (II)-, Chromium (III)- and Europium (III)- Tricarballylic acid (TCA) Moiety of Mycotoxin Natural Products

The coordination behavior of nickel (II) chromium (III) and europium (III) with tricarballylic acid (TCA) is described. Three new compounds Ni(II)-TCA, Cr(III)-TCA and Eu(III)-TCA were obtained and characterized of the species by elemental analysis, thermal behavior of TGA, DTA, DSC, IR and magnetic susceptibility.