Mohamed Ibrahim Mohamed Tahir

Synthesis, antibacterial activity and cytotoxicity of new fused pyrazolo (1,5-a)pyrimidine and pyrazolo(5,1-c)(1,2,4)triazine derivatives from new 5-aminopyrazoles

New 5-aminopyrazoles 2a-c were prepared in high yields from the reaction of known α,α-dicyanoketene-N,S-acetals 1a-c with hydrazine hydrate under reflux in ethanol. These compounds were utilized as intermediates to synthesize pyrazolo[1,5-a]-pyrimidines 3a-c, 4a-d, 5a-c, and 6a-c, as well as pyrazolo[5,1-c][1,2,4]triazines 7a-c and 8a-c, by the reaction of 2-[bis(methylthio)methylene]malononitrile, α,α-dicyanoketene-N,S-acetals 1a-b, acetylacetone, acetoacetanilide as well as acetylacetone, and malononitrile, respectively. Furthermore, cyclization of 2a-c with pentan-2,5-dione yielded the corresponding 5-pyrrolylpyrazoles 9a-c. Moreover, fusion of 2a-c with acetic anhydride resulted in the corresponding 1-acetyl-1H-pyrazoles 10a-c. The antibacterial activity and cytotoxicity against Vero cells of several selected compounds are also reported.

Synthesis, characterization and biological evaluation of transition metal complexes derived from N, S bidentate ligands.

Two bidentate NS ligands were synthesized by the condensation reaction of S-2-methylbenzyldithiocarbazate (S2MBDTC) with 2-methoxybenzaldehyde (2MB) and 3-methoxybenzaldehyde (3MB). The ligands were reacted separately with acetates of Cu(II), Ni(II) and Zn(II) yielding 1:2 (metal:ligand) complexes. The metal complexes formed were expected to have a general formula of [M(NS)2] where M = Cu2+, Ni2+, and Zn2+. These compounds were characterized by elemental analysis, molar conductivity, magnetic susceptibility and various spectroscopic techniques. The magnetic susceptibility measurements and spectral results supported the predicted coordination geometry in which the Schiff bases behaved as bidentate NS donor ligands coordinating via the azomethine nitrogen and thiolate sulfur. The molecular structures of the isomeric S2M2MBH (1) and S2M3MBH (2) were established by X-ray crystallography to have very similar l-shaped structures. The Schiff bases and their metal complexes were evaluated for their biological activities against estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) breast cancer cell lines. Only the Cu(II) complexes showed marked cytotoxicity against the cancer cell lines. Both Schiff bases and other metal complexes were found to be inactive. In concordance with the cytotoxicity studies, the DNA binding studies indicated that Cu(II) complexes have a strong DNA binding affinity.

New insight into the structural, electrochemical and biological aspects of macroacyclic Cu(II) complexes derived from S-substituted dithiocarbazate schiff bases

Copper (II) complexes synthesized from the products of condensation of S-methyl- and S-benzyldithiocarbazate with 2,5-hexanedione (SMHDH2 and SBHDH2 respectively) have been characterized using various physicochemical (elemental analysis, molar conductivity, magnetic susceptibility) and spectroscopic (infrared, electronic) methods. The structures of SMHDH2, its copper (II) complex, CuSMHD, and the related CuSBHD complex as well as a pyrrole byproduct, SBPY, have been determined by single crystal X-ray diffraction. In order to provide more insight into the behaviour of the complexes in solution, electron paramagnetic resonance (EPR) and electrochemical experiments were performed. Antibacterial activity and cytotoxicity were evaluated. The compounds, dissolved in 0.5% and 5% DMSO, showed a wide range of antibacterial activity against 10 strains of Gram-positive and Gram-negative bacteria. Investigations of the effects of efflux pumps and membrane penetration on antibacterial activity are reported herein. Antiproliferation activity was observed to be enhanced by complexation with copper. Preliminary screening showed Cu complexes are strongly active against human breast adenocarcinoma cancer cell lines MDA-MB-231 and MCF-7.

Synthesis of Some Novel α-Cyanoketene-N,S-acetals Derived from Secondary Aliphatic Amines and Their Use in Pyrazole Synthesis

Abstract New α-cyanoketene-N,S-acetals 2(a–g) and β-dialkylamine-α-cyanoacrylates 3(g–i) were synthesized in good to excellent yields by the reaction of ethyl 2-cyano-3,3-bis(methylthio)acrylate 1 with secondary aliphatic amines (i.e., N-methylalkyl- and N-ethylalkylamines), and pyrrolidine, in the presence of triethylamine, under reflux in ethanol, for 1–16 h, depending on the amine used. Five N-methylalkyl amines and pyrrolidine yielded exclusively mono-substituted N,S-acetals 2(a–f) in good yields. On the other hand, N-ethylbenzylamine gave a mixture of monosubstituted products including N,S-acetal 2g in 35% yield and the unexpected product ethyl 3-[benzyl(ethyl)amino]-2-cyanoacrylate 3g in 50% yield. N-Ethylcyclohexylamine and N-ethylbutylamine did not produce N,S-acetals and gave only the unexpected products ethyl 2-cyano-3-[cyclohexyl(ethyl)amino]acrylate 3h and ethyl 3-[butyl(ethyl)amino]-2-cyanoacrylate 3i in good yields. The α-cyanoketene-N,S-acetals 2(a–f), 2j, and 2k underwent cyclization with the binucleophile hydrazine in ethanol under reflux to afford substituted pyrazoles 4(a–f), 4j, and 4k in good yields. [Supplementary materials are available for this article. Go to the publishers online edition of Synthetic Communications® for the following free supplemental resources: Full experimental and spectral details.] GRAPHICAL ABSTRACT

2-Cyclo-hexyl-idene-N-methyl-hydrazine-carbothio-amide.

The title compound C8H15N3S has two molecules in the asymmetric unit in which cis–trans isomerism is exhibited around the N(NH)C=S bonds. The cyclohexyl rings in both molecules adopt a chair conformation. In the crystal, N—H⋯S hydrogen bonding produces dimers, which are interconnected through further N—H⋯S hydrogen bonds, forming chains along the b-axis direction.

1,1-Diethyl-3-(4-meth­oxy­benzo­yl)thio­urea

In the title compound, C13H18N2O2S, the 4-methoxybenzoyl fragment is approximately planar [maximum deviation = 0.057 (2) Å] and twisted relative to the thioamide fragment, forming a dihedral angle of 86.62 (6)°. The two Csp 2—Nsp 2 bonds in the thiourea unit differ significantly in length [1.327 (2) and 1.431 (2) Å]. In the crystal, N—H⋯O hydrogen bonds link the molecules into chains parallel to [010].

(N-Benzyl-N-isopropyl­dithio­carbamato)chloridodiphenyl­tin(IV)

The SnIV atom in the title organotin dithiocarbamate, [Sn(C6H5)2(C11H14NS2)Cl], is penta-coordinated by an asymmetrically coordinating dithiocarbamate ligand, a Cl and two ispo-C atoms of the Sn-bound phenyl groups. The resulting C2ClS2 donor set defines a coordination geometry intermediate between square-pyramidal and trigonal-bipyramidal with a slight tendency towards the latter. The formation of close intramolecular C–H⋯Cl and C–H⋯S contacts precludes the Cl and S atoms from forming significant intermolecular contacts. The presence of C–H⋯π contacts leads to the formation of supramolecular arrays that stack along the b axis.

Crystal structure of benzyl (E)-2-(3,4-di-meth-oxy-benzyl-idene)hydrazine-1-carbodi-thio-ate.

In the crystal of the title compound, which crystallized with two independent molecules (A and B) in the asymmetric unit, the A and B molecules are linked via pairs of N—H⋯S hydrogen bonds, forming dimers with an (8) ring motif. The dimers are linked via pairs of C—H⋯O hydrogen bonds and C—H⋯π interactions, forming ribbons propagating along [100].

(Pyridin-4-yl)methyl N′-(3-phenyl­allyl­idene)hydrazinecarbodithio­ate

In the title compound, C16H15N3S2, the central C2N2S2 residue is planar (r.m.s. deviation = 0.045 Å) and the pyridyl and benzene rings are inclined and approximately coplanar to this plane, respectively [dihedral angles = 72.85 (9) and 10.73 (9)°], so that, overall, the molecule adopts an L-shape. The conformation about each of the N=C [1.290 (3) Å] and C=C [1.340 (3) Å] bonds is E. Supramolecular chains along [1-10] are stabilized by N—H⋯N(pyridine) hydrogen bonding and these are connected into a double layer that stacks along the c-axis direction by C—H⋯π(pyridine) interactions.

Di-n-butyl-bis-(N-ethyl-N-phenyl-dithio-carbamato-κS)tin(IV).

The title compound, [Sn(C4H9)2(C9H10NS2)2], features a tetrahedrally coordinated SnIV atom; the dithiocarbamate ligands coordinate in a monodentate fashion, accompanied by two n-butyl chains. The non-coordinating thione S atoms are each proximate to the SnIV atom [3.0136 (7) and 2.9865 (8) Å], giving rise to distortions from the ideal geometry as evident in the wide C—Sn—C bond angle of 139.06 (12) °. In the crystal, C—H⋯S interactions lead to the formation of a linear supramolecular chain along the b axis. The chains are aligned into layers by C—H⋯π interactions, and the layers stack along [001]. One of the ethyl groups is statistically disordered over two sets of sites.