The reaction of cyanoacetyl hydrazine (1) with 3-acetylpyridine (2) gave the hydrazide-hydrazone derivative 3. The latter compound undergoes a series of heterocyclization reactions to give new heterocyclic compounds. The antitumor evaluation of the newly synthesized products against three cancer cell lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) was performed. Most of the synthesized compounds showed high inhibitory effects.

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Novel azaenamines incorporating a tetrahydrothiophene moiety were prepared. Michael addition of an azaenamine with a,bunsaturated nitriles took place to give [1]benzothieno[3¢,2¢:5,6]pyrimido[1,2-b]pyridazine (thia-triaza-benzo[a]fluorene) derivatives. The condensation with malononitrile resulted in the formation of a [1]benzothieno[3¢,2¢:5,6]pyrimido[1,2-b]pyridazine-4-carbonitrile. The azaenamine also reacted with aldehydes and piperidine to give Mannich products.Compounds containing the tetrahydrobenzothiophene (THBT) moiety are selective HCV polymerase inhibitors, 1 selective versus human DNA polymerase and calf thymus. 1 These compounds also have diverse pharmacological activities including antibacterial, 2 immunodulatory, 3 anti-inflammatory, 4 antidiabetic, antiplatelet activating factor, 5 and antiviral activity. 6,7 In continuation of our interest in azaenamine chemistry, [8][9][10][11][12] we report here a new synthesis of azaenamines containing the 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate and -carboxamide moieties. Also we report the chemical reactivity of the synthesized azaenamines. Thus, it has been found that coupling acetoacetic acid with the 3-(ethoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-diazonium chloride (3a) and the 3-carboxamide 3b afforded the corresponding pyruvaldehyde-1-arylhydrazones 5a and 5b in 73% and 68% yields, respectively. Although, the appearance of NH at very low field implies the presence of an azaenamine in the syn-form 6, in related work we obtained an X-ray crystal structure for an azaenamine analogue that indicated that it exists in the antiform 5. 10 The low field hydrazone NH at d = 12 is not, thus, due to deshielding by hydrogen bonding as we believed, but most likely results from the delocalization of the nitrogen lone pair [cf. Scheme 1 structure 5(II)]. It is clear that azaenamines can be seen as bidentate ligands since they have two nucleophilic and two electrophilic centers. Due to an interest in developing syntheses for biologically interesting fused pyridazines 8,12,13 herein, we report an efficient route for the Michael addition reaction of azaenamines 5 to a,b-unsaturated nitriles. As stated above, the CH group of the azaenamine is quite nucleophilic as a result of the hydrazone lone pair delocalization. Thus, in a preliminary study, we found that reacting compound 5a with ethyl 2-cyano-3-phenylacrylate (7a) afforded a product for which several isomeric structures seemed possible. Structures involving addition on the acyl methyl group was readily ruled out on the basis of the 1 H NMR spectrum, which revealed a methyl signal at d = 2.36. Acyclic structures were also excluded based on 1 H NMR spectra analysis, which showed in addition to the methyl signal, a singlet signal at d = 5.09 for H4 of the pyridazine and a broad signal at d = 11.19 for the NH group. The resulting product was assigned the tetracyclic structure 10 based on mass spectroscopy and NMR analysis, which revealed the absence of an OEt group on the thiophene ring. IR and 13 C NMR...

This paper describes a novel combined post-extraction process for obtaining bioactive compounds from the aqueous high molecular weight sulfated polysaccharides (SPs) extracts of the green algae, Ulva lactuca. After extracting the SPs, they were enzymatically hydrolyzed then the hydrolysate (V45) was fractionated into eight different molecular weight fractions (F1–F8) using ion exchange chromatography. Crude SPs together with V45 and (F1–F8) were examined for their carbohydrate, protein, and sulfate contents. In addition, their degree of polymerization (DP) was estimated and they were characterized by Fourier Transform Infrared Spectroscopy (FTIR). Fractions S1, F4, F5, and F8 showed promising antioxidant and antitumor activities in vitro. In particular, the remarkable antitumor activity of F5 on three types of cancer cell lines could be attributed to its comparable contents of protein, carbohydrate, and sulfate, in addition to its comparable contents of rhamnose and glucuronic acid, and the same for glucose and arabinose. F5 also possessed the highest Hill coefficient among the four promising fractions indicating a higher degree of cooperativity in ligand binding. Other influencing factors including DP, composition, and type of characteristic functional groups were also discussed. The implications of this work could potentially benefit the industries of food supplements and pharmaceuticals.

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