ElSayed M. Shalaby

Regioselective synthesis and theoretical studies of an anti-neoplastic fluoro-substituted dispiro-oxindole

Single crystal X-ray studies of regioselectively synthesized fluoro-substituted dispiro-oxindole 9 revealed that the structure belongs to the monoclinic space group P21/n with four molecules in the unit cell. The structure was also investigated by AM1, PM3, and DFT studies. Compound 9 exhibits high potency against the HeLa cell line.

Synthesis and DFT studies of an antitumor active spiro-oxindole

An anti-oncological active spiro-oxindole 7 was synthesized regioselectively via a [3+2]-cycloaddition reaction of azomethine ylide to exocyclic olefinic linkage of 4-piperidone 6, exhibiting properties against diverse tumor cell lines including leukemia, melanoma and cancers of the lung, colon, brain, ovary, breast, prostate, and kidney. Compound 7 crystallizes in the monoclinic system and P21/c space group with four molecules in the unit cell. The structure was also studied by AM1, PM3 and DFT techniques. DFT studies support the stereochemical selectivity of the reaction and determine the molecular electrostatic potential and frontier molecular orbitals.

Synthesis and molecular modeling studies of indole-based antitumor agents

Indole-based compounds 30–63 were synthesized by the multi-component 1,3-dipolar cycloaddition reaction of 1-alkyl-3,5-bis(arylidene)-4-piperidones 11–25 with azomethine ylides (generated by the condensation of isatins 26–28 with sarcosine 29). The single crystal X-ray studies of 46 and 48 supported the regio- and stereoselectivity of the reaction. Most of the synthesized spiro-indoles exhibited potent antitumor properties against the HeLa (cervical cancer) cell line through in vitro sulfo-rhodamine-B bioassay, higher than that of cisplatin. Only compound 54 showed bio-potency against the HepG2 (hepatocellular cancer) cell line, comparable to that of doxorubicin hydrochloride (standard reference). 3D-Pharmacophore and 2D-QSAR studies were used to validate the observed biological data and determine the most important parameters controlling activity. The estimated bio-properties from the computational studies showed high approximations to the experimental data.

Molecular structure studies of novel bronchodilatory-active 4-azafluorenes

Abstract Two 5H-indeno[1,2-b]pyridines, 7a and 7b, were synthesized and characterized by X-ray crystallography. In the molecular packing, molecules of 7a are linked into chains by C–H···N hydrogen bond which, in turn, are connected by H···π, N···π, Cl···π and π···π interactions. In the crystal structure of 7b, molecules are connected by C–H···N and C–H···Cl interactions as well as a set of N···π and Cl···π interactions. The molecular structures were studied by theory using AM1, PM3 and DFT. The basic difference between the theoretical and experimental structures was found in the relative orientation of dichlorophenyl ring attached to the indenopyridine residue, which was revealed to be aligned in nearly opposite orientations. This observation is attributed to the bulky chlorine atom(s) of the phenyl ring that prevent free rotation around the sigma bond attaching this ring with the heterocyclic system. DFT was used to determine the molecular electrostatic potential revealing the nitrile nitrogen to be the most nucleophilic site. A low HOMO-LUMO energy gap indicates high reactivity of 7a and 7b. The synthesized azafluorenes show more potent bronchodilation properties than the standard reference compound (theophylline).

Rational design, synthesis and 2D-QSAR studies of antiproliferative tropane-based compounds

3,4-Diaryl-11-methyl-7-[(aryl)methylidene]-4,5,11-triazatricyclo[6.2.1.0*2,6*]undec-5-enes 14a–s were synthesized through reaction of 2,4-bis[(aryl)methylidene]-8-methyl-8-azabicyclo[3.2.1]octan-3-ones 12a–f with aryl hydrazines in the presence of catalytic amount of thiamine hydrochloride. Meanwhile, the 4-acetyl analogs 16a,b were obtained through reaction of 12b,e and hydrazine hydrate in acetic acid. Good support for the structure was received from single crystal X-ray studies of 14a. Some of the synthesized tropane containing-compounds showed promising antitumor properties during the in vitro MTT bio-assay against HepG2 (hepatocellular) and MCF7 (breast) human tumor carcinoma cell lines, with potency higher than that of doxorubicin (DNA intercalating agent, standard reference). Statistically significant 2D-QSAR model describes the antitumor properties against MCF7.

Crystal Structure Studies and Bronchodilation Properties of Novel Benzocycloheptapyridines

Benzocycloheptapyridines 6a and 6b were characterized by single crystal X-ray diffraction. Molecular packing exhibits that, molecules of compound 6a are linked in chains by one hydrogen bond of C–H···N type and set of H–π, and Cl–π interactions. However, compound 6b is stabilized by only Cl–π interactions. The main conformational difference between the experimental and theoretical optimized structures (using AM1, PM3 and DFT) was found in the relative orientation of the dichlorophenyl ring attached to the benzocycloheptapyridine system, which is attributed to the effect of the bulky chloride atom that prevents free rotation around the sigma bond attaching this ring with the heterocyclic system. Also, the lattice form plays an important role affecting the observed conformation. A similar behavior is also exhibited for the methyl group of the ethoxy function of 6b. The synthesized 6a reveals bronchodilation potency greater than that of the standard reference used, theophylline.Graphical AbstractBenzocycloheptapyridines were characterized by single crystal X-ray diffraction. Computational chemistry studies (AM1, PM3 and DFT) support the molecular structures. The synthesized analogues reveal promising bronchodilation properties.

Crystal Structure and Stereochemistry Study of 2-Substituted Benzoxazole Derivatives

The structure of 2-[(4-chlorophenylazo) cyanomethyl] benzoxazole, C15H9ClN4O (I), has triclinic (P1®) symmetry. The structure displays N–H ⋯ N hydrogen bonding. The structure of 2-[(arylidene) cyanomethyl] benzoxazoles, C17H10N2O3 (II), has triclinic (P1®) symmetry. The structure displays C–H ⋯ N, C–H ⋯ C hydrogen bonding. In (I), the chlorophenyl and benzoxazole groups adopt a trans configuration with respect to the central cyanomethyle hydrazone moiety. Compound (II) crystallized with two molecules in the asymmetric unit shows cisoid conformation between cyano group and benzoxazole nitrogen, contrary to (I). In (II) the benzodioxole has an envelope conformation (the C17 atom is the flap atom). The molecular geometry obtained using molecular mechanics (MM) calculations has been discussed along with the results of single crystal analysis.

Synthesis, X-ray powder diffraction and DFT calculations of vasorelaxant active 3-(arylmethylidene)pyrrolidine-2,5-diones

Two 3-(arylmethylidene)pyrrolidine-2,5-diones, 12a and 12b, were synthesized and characterized by powder X-ray diffraction utilizing a high-resolution synchrotron X-ray powder technique. The basic difference between the theoretical (AM1, PM3 and DFT computational studies) and experimental (X-ray diffraction) structures is the relative orientation of aryl groups attached to the pyrrolidinyl nitrogen and exocyclic olefinic linkage. The lattice form controlling the X-ray structure is responsible for these observations. Pyrrolidines 12a, b reveal vasodilation bio-properties with potency higher than that of doxazosin (clinically applicable α1-adrenergic receptor blocker).

Crystal Structure and Molecular Mechanics Modelling of 2-(4-Amino-3-benzyl-2-thioxo-2,3-dihydrothiazol-5-yl)benzoxazole

The crystal structure of the title compound, 2-(4-amino-3-benzyl-2-thioxo-2,3-dihydrothiazol-5-yl)benzoxazole, was determined. The crystal has P1 space group and triclinic system with unit cell parameters a = 5.174(3) A, b = 6.411(6) A, c = 12.369(10) A, α = 86.021(4)°, β = 84.384(5)°, and γ = 77.191(5)°. The structure consists of benzoxazole group connected with benzyl via thiazole (attached with amino and thione). Benzoxazole and thiazole rings are almost planar (maximum deviation at C1, −0.013(3) A, and C10, 0.0041(3) A, resp.). The phenyl ring is nearly perpendicular to both thiazole and benzoxazole rings. A network of intermolecular hydrogen bonds and intermolecular interactions stabilizes the structure, forming parallel layers. The molecular geometry obtained using single crystal analysis is discussed along with results of the molecular mechanics modeling (MM), and the results showed the same cis conformation between benzoxazole nitrogen atom and the amino group.

Crystal Structures of Ethyl 4-(4-Florophenyl)-6-phenyl-2-substituted-3-pyridinecarboxylates

Three substituted pyridinecarboxylates were synthesized; (I) ethyl 2-bromo-4-4(fluorophenyl)-6-phenyl-3-pyridinecarboxylate, C20H15BrFNO2, (II) ethyl 4-(4-fluorophenyl)-2-(4-morpholinyl)-6-phenyl-3-pyridinecarboxylate, C24H23FN2O3, and (III) ethyl 4-(4-fluorophenyl)-6-phenyl-2-(1-piperidinyl)-3-pyridinecarboxylate, C25H25FN2O2. It was found that compound (I) belongs to the orthorhombic system with space group P212121, compound (II) to the monoclinic system with space group P21/c, and compound (III) to the monoclinic system with space group C2/c. The morpholine ring in (II) and piperidine ring in (III) have the shape of the distorted chair configuration.