Rasha A. Azzam

Heterocyclic ring extension of estrone: Synthesis and cytotoxicity of fused pyran, pyrimidine and thiazole derivatives

The one pot reaction of estrone with the aromatic aldehydes 2a-c and either of malononitrile or ethyl cyanoacetate afforded the fused pyran derivatives 4a-f. On the other hand, carrying the same reaction using thiourea instead of the cyanomethylene reagent gave the fused pyrimidine derivatives 6a-c. The latter compounds reacted with phenacyl bromide to give the thiazolo[3,2-a]pyrimidine derivatives 8a-c. The reaction of the title compound with bromine gave the monobromo derivative 13 which in turn reacted with either thiourea or cyanothioacetamide to give the thiazole derivatives 14 and 16, respectively. The cytotoxicity of the newly synthesized products was evaluated against six human cancer and normal cell lines where the results showed that compounds 4c, 4f, 6b, 8b, 8c, 10, 13, 16, 18c and 19c exhibited optimal cytotoxic effect against the cancer cell lines, with IC50s in the nM range.

Antimetabolites: A First Synthesis of a New Class of Cytosine Thioglycoside Analogs

Abstract A first synthesis of a new class of novel cytosine thioglycoside analogs from readily available starting materials has been described. The key step of this protocol is the formation of sodium pyrimidine-4-thiolate via condensation of N′-arylidene-2-cyanoacetohydrazides with sodium cyanocarbonimidodithioate salt, followed by coupling with halo sugars to give the corresponding cytosine thioglycoside analogs. Ammonolysis of the latter compounds afforded the free thioglycosides.

Crystal structure of N-[6-amino-5-(benzo[d]thia­zol-2-yl)-3-cyano-4-methyl­sulfanyl-2-oxo-1,2-di­hydro­pyridin-1-yl]-4-methyl­benzene­sulfonamide di­methyl­formamide monosolvate

In the title compound, the toluenesulfonamide ring and the combined ring system involving the pyridone and benzothiazole rings subtend an interplanar angle of 39.86 (4)°. The pyridone and benzothiazyl rings are linked by an intramolecular N—Hamine⋯Nthiazole hydrogen bond. The molecules are linked by hydrogen bonds and an S⋯O contact to form layers parallel to the bc plane.

Influence of Crosslink Characteristics Induced by Aromatic-Based Antioxidants on the Swelling and Stress-Strain Behavior of Natural Rubber Vulcanizates

Stress-strain measurements were performed on dry and swollen natural rubber vulcanizates prepared using both sulfur as the crosslinking agent and aromatic-based bound antioxidants acting as a second crosslinking agent. The aromatic-based antioxidants were synthesized and analyzed spectroscopically in order to relate the final behavior of the vulcanizates to the nature of the crosslink characteristics. The anomalous upturn in the modulus values of these networks in response to the imposed stress was shown to persist in the dry as well as the swollen state. Since the swollen elastomeric chains cannot undergo a strain-induced crystallization, the abnormal upturns in the modulus values in an absence of a filler were explained on the basis of the limited extensibility of the short chains of networks prepared using two different crosslinking agents in line with earlier modeling predictions. Remarkably, the swelling experiments revealed the increase in the crosslink density of the networks in the early stages of the thermal oxidative degradation procedure indicating a post-cure of the chemically bound antioxidants to the elastomeric chains, which incidentally corresponds to a maximum in the modulus values of the networks. The rheological and other mechanical properties such as the hardness were shown not to have been affected as a result of the incorporation of the chemically bound antioxidants.

Imide-Based Polymers of Intrinsic Microporosity: Probing the Microstructure in Relation to CO2 Sorption Characteristics

A range of microporous, imide-based polymers were newly synthesized using two-step poly-condensation reactions of bis(carboxylic anhydride) and various aromatic diamines for CO2 gas capture and storage applications. In this report, we attempted to assess the relative significance of molecular structural aspects through the manipulation of the conformational characteristics of the building blocks of the polymeric structures, the spiro-containing acid anhydride and the aromatic amines, to induce greater intrinsic microporosity and higher surface areas for the resulting solids. Results obtained from this study were thus used to outline a working relationship between the structural diversity of the constructed porous solids and their performance as CO2 sorbents.

Crystal structure of N′-[2-(benzo[d]thia­zol-2-yl)acet­yl]-4-methyl­benzene­sulfono­hydrazide

In the title compound, the hydrazide N atom bonded to the C=O group is planar, whereas that bonded to the SO2 group is pyramidally coordinated. The interplanar angle between the ring systems is 40.71 (3)°. In the crystal, molecules are connected by N—H⋯O=C and N—H⋯Nthiazole hydrogen bonds, forming ribbons parallel to the b axis.

Crystal structure of 2-cyano-3,3-bis­(ethyl­sulfan­yl)-N-o-tolyl­acryl­amide

In the molecule of the title compound, the central S2C=C(CN)C moiety is planar (r.m.s. deviation = 0.029 Å). The C=O and C—CN groups are trans to each other across their common C—C bond. In the crystal, one classical and two ‘weak’ hydrogen bonds combine with borderline N⋯N and S⋯S contacts to form layers parallel to (10).

Multicomponent Reactions of Acetoacetanilide Derivatives with Aromatic Aldehydes and Cyanomethylene Reagents to Produce 4H-Pyran and 1,4-Dihydropyridine Derivatives with Antitumor Activities

The multi-component reaction of either acetoacetanilide derivative 1a or b with any of the aldehyde derivatives 2a-d and malononitrile 3 in the presence of triethylamine as a catalyst gave the 4H-pyran derivatives 4a-g, respectively. Carrying the same reaction but using a catalytic amount of ammonium acetate gave the 1,4-dihydropyridine derivatives 5a-f, respectively. The use of ethyl cyanoacetate instead of malononitrile in the presence of a catalytic amount of triethylamine gave the 4H-pyran derivatives 7a-d, respectively. Compound 4e was used to synthesize 1,4-dihydropyridine 9a-c and arylhydraone 11a-e derivatives were synthesized from 4a and e. The anti-tumor evaluations of the newly synthesized products were tested against six human cancer and normal cell lines. The results showed that compounds 4a, b, f, 5d, f, 9 and 11a-d had optimal cytotoxic effect against cancer cell lines with IC50<550 nM. The toxicity of the most active compounds was further measured against shrimp larvae.