Hala M. Aly

Design and synthesis of some new thiophene, thienopyrimidine and thienothiadiazine derivatives of antipyrine as potential antimicrobial agents.

4-acetamide Pyrazolone 2 was synthesized by acetylation of 4-amino antipyrine 1 in excellent yield. 4-acetamide pyrazolone 2 was exploited as a starting material for the syntheses of hitherto unknown different types of new heterocyclic compounds incorporating the antipyrine moiety which expect highly biological activity against various microorganisms. Thus, Claisen condensation of 4-acetamide pyrazolone 2 with diethyl oxalate have been utility to afford new 4-oxaloacetyl antipyrine 3, which upon hydrazinolysis of the ester function to obtain the acetohydrazide derivative 18 which used as starting material to synthesize 1,2,4-triazol 19 and hydrazone 20 derivatives. 4-aminothiophene carboxylate derivatives 6, 7 were synthesized by utility of Gewald reaction. On the other hand, Michael type addition of the enolate ion of acetyl functions in acetamide pyrazolone 2 to the activated double bond in arylidenemalonoester to furnish pyrane derivative 9 was done. Finally, 4-acetamide pyrazolone 2 was treated with aromatic substituted aldehyde to exhibit thiophenacrylamide derivative 10. Compound 6 gave characteristic reaction for enaminonitriles, thus, the behavior of o-aminoester of 4-aminothiophene carboxylate derivative 6 toward electrophilic reagent, one carbon donars, amide and acid was also investigated to afford the correspondence thiophene derivatives 11,12,13,15 and 16. In addition, treatment of carboxamide derivative 16 with thionyl chloride afforded the thienothiadiazine derivative 17. The characterization of all synthesized compounds was done by elemental analysis and spectral studies. Moreover, all the synthesized compounds were tested against antimicrobial activities by the disc diffusion method, which exhibited higher promising biological activities.

Synthesis and Biological Activity of Some Novel Thieno[2,3-b]quinoline, Quinolino[3′,2′:4,5] thieno[3,2-d]pyrimidine and Pyrido[2′,3′:4,5] thieno[2,3-b]quinoline Derivatives

Thieno [2,3-b] quinoline derivative 5 was synthesized by the cycloalkylation of compound bi 3a with chloro acetonitrile. Interaction of compound 5 with formic acid, formamide, and thioacetamide furnished the corresponding quinolino[3′,2′:4,5]thieno[3,2- d]pyrimidine derivatives 7 , 8 , and 9 , respectively. Also, quinolinothienopyrimidine 11 was obtained in good yield by cyclization of compound 5 with phenyl isothiocyanate under reflux in pyridine. Triethyl orthoformate reacted with compound 5 to form the ethoxymethylene derivative 12 . Refluxing of 5 with acetic anhydride for a short time afforded acetamide derivative 16 , whereas when refluxed for a long time furnished the diacetyl derivative 17 . Fusion of compound 5 with urea and thiourea yielded the corresponding quinolinothienopyrimidines 19 and 20 , respectively. When compound 5 was reacted with urea in the presence of sodium ethoxide, the corresponding ureado derivative 18 was obtained. Treatment of 5 with sulfuric acid at r.t. furnished the novel thienoquinoline 6 , while on heating gave the acid derivative 21 . Pyrido [2′,3′: 4,5]thieno [2,3- d] quinoline 23–25 were synthesized by the interaction of 5 with ethyl cyanoacetate, benzylidenemalononitrile, and acetaldehyde/malononitrile, respectively. On preliminary screening, compounds 22 and 25 exhibited in vitro growth that was inhibitory activity against Saccharomyces Cerevisiae when compared with the standard fungicide Mycostatine. The structure of the biologically active compounds 22 and 25 remain unchanged when exposed to gamma irradiation up to 40 KGy.

Synthesis of Thiazolidine and Thiophene Derivatives for Evaluation as Anticancer Agents

The non-isolated adducts (3a,b) were used as key intermediates to synthesize some novel thiazolidine and thiophene derivatives. Compound (4) exhibited a remarkable antitumor activity against EAC cells compared with the Doxorubicin as a positive control.

Novel Pyrazole Derivatives as Anticancer and Radiosensitizing Agents

The present article describes the synthesis of some novel pyrrole, pyrazolo[4,3-d]oxazole, pyrrolo[2,3-b]pyridine, 1,2,3-triazole and oxoazetidin derivatives incorporating pyrazole moiety, the structures of which were confirmed by elemental analyses and spectral data. All the target compounds were subjected to in-vitro antitumor activity against liver and colon human tumor cell lines (HEPG2 and HCT), furthermore, the most potent compounds were evaluated for their ability to enhance the cell killing effect of γ-radiation (radiosensitizing evaluation). The results of in-vitro anticancer evaluation showed that compounds 3 and 16a were the most potent compounds on HEPG2 (IC50=2.6 and 4.2 µg/ml) and compounds 2 and 10 were the most potent on HCT (IC50=2.7 and 3.9 µg/ml) compared to vinblastine (IC50=4.6 on HEPG2 and 2.6 µg/ml on HCT), while, the activity of the most potent compounds increased after combination with γ-radiation and they showed no toxicity on normal hepatocytes and colon cells at their effective concentrations.

Antitumor Activity of Some Novel 1,2,5-Thiadiazole Derivatives

Some novel thiourea,1,2,4-triazole, quinazoline, thieno[2,3-d]pyrimi-dine, and thiazolidine derivatives were synthesized to evaluate their antitumor activity. Compound (3f) is nearly as active as reference drug, (Doxorubicin) as positive control.

Synthesis and Antitumor Activity of Some Novel Pyrazole and Thienopyrimidine Derivatives

The novel thiosemicarbazide derivative was prepared by hydrazinolysis of isothiocyanatosulfonamide with hydrazine hydrate. It was used as a starting material for the synthesis of some novel pyrazolosulphaphenazole, phthalazine, thiourea, and 1,2,4-triazolbenzenesulfonamide derivatives. Isothiocyanato sulfonamide was cyclized with sulfanyl acetic acid to furnish the novel 2-thioxothiazolidine derivative. Treatment of p-substituted sulfamoylphenyl isothiocyanate derivatives with various O-aminoesters of thiophene derivatives yielded dimethyl thiophene-carboxylate, methylthiophene carboxylate, and thienopyrimidine derivatives. Some of synthesized compounds were evaluated for one cell line. Compounds 3, 9, 15a, 15b, and 18 exhibited remarkable antitumor activity against MCF7 (breast) human cells. Supplemental materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Synthesis of bifunctional thieno[3,2-c]pyrazole, pyrazolothieno[2,3-d]pyrimidin derivatives and their antimicrobial activities

A simple and convenient route was performed for the synthesis of some new heterocyclic compounds based on thieno[3,2-c]pyrazole derivative for antimicrobial evaluation. The key intermediate, 5-amino-3-methyl-1-phenyl-1H-thieno[3,2-c]pyrazole-6-carbohydrazide 3, was prepared by Gewald’s synthesis of Ethyl 5-amino-3-methyl-1-phenyl-1H-thieno[3,2-c]pyrazole-6-carboxylate 2. This intermediate reacted with various reagents to afford different fused and polyfunctional substituted. The structures of these compounds were confirmed by elemental analysis, IR, 1H NMR, 13C NMR and mass spectral data. All the new synthesized compounds were screened for various microorganisms such as Aspergillus fumigatus; Geotrichum candidum; Syncephalastrum racemosum (Fungus); Candida albicans (Yeast fungus); Staphylococcus aureus; Bacillus subtilis (as Gram-positive bacteria); Pseudomonas aeruginosa and Escherichia coli (as Gram-negative bacteria) by the disc diffusion method. In general, the novel synthesized compounds possessed moderate to high antimicrobial activity against the previously mentioned microorganisms.

Novel Antitumor Acetamide, Pyrrole, Pyrrolopyrimidine, Thiocyanate, Hydrazone, Pyrazole, Isothiocyanate and Thiophene Derivatives Containing a Biologically Active Pyrazole Moiety

4-Amino-N-(1-phenyl-1H-pyrazol-5-yl)-benzenesulfonamide (sulfaphenazole) 1 was selected as strategic starting material for the synthesis of some novel acetamide 2, pyrrole 4, pyrrolo[2,3-d]pyrimidine 5, thiocyanate 6, hydrazone 7a,b pyrazole 8, isothiocyanate 9 and thiophene 12 derivatives to evaluate theantitumor activity. Compound 4 was more effective than the reference drug, doxorubicin (CAS 23214-92-8) as positive control.

Synthesis, structural characterization and anticancer evaluation of pyrazole derivatives

The utility of 4-isothiocyanato-N-(1-phenyl-1H-pyrazol-5-yl)benzene sulfonamide 2 in the synthesis of some novel thiosemicarbazide, carbamothioate,1,3,4-thiadiazole, azomethine, thiourea, bisthiourea and imidazole derivatives is reported. The structure of the newly synthesized compounds was confirmed on the basis of analytical and spectral data. Some of the prepared compounds were evaluated for their in vitro anticancer activity against Ehrlich ascites carcinoma cells (EAC). It was found that the corresponding 2-acetyl-N-(4-(N-(1-phenyl-1H-pyrazol-5-yl) sulfamoyl)phenyl) hydrazinecarbothioamide 7 with IC50 value (2.14 µg/ml) showed better activity than doxorubicin with IC50 value (43.6 µg/ml) as reference drug.Graphical AbstractNew thiosemicarbazide,carbamothioate,1,3,4-thiadiazole, azomethine, thiourea, bisthiourea and imidazole derivatives containing pyrazole moiety have been synthesized and evaluated for their anticancer activity.

Efficient procedure with new fused pyrimidinone derivatives, Schiff base ligand and its La and Gd complexes by green chemistry

In this study, a convenient synthesis of a series of pyrimido[4,5-d]pyrimidine, pyrimidine acetohydrazide, and thieno[3,2-d]pyrimidine-7-carbohydrazide derivatives, via the reactions of versatile, readily accessible electrophilic and nucleophilic reagents with 2-thioxodihydropyrimidine-4,6(1H,5H)-dione 1, is described. Different biologically active moieties such as thiophene and pyridine are introduced in order to investigate their anticancer activity in vitro. In addition, a Schiff base ligand derived from the reaction of 5-bromosalicylaldehyde with 6-aminothieno[3,2-d]pyrimidine carbohydrazide 8 and its La(III) and Gd(III) complexes (in the bulk and at the nanoscale) were prepared and characterized by elemental analyses, IR spectra, magnetic measurement, and electronic absorption data. Chemical shifts of the different types of protons in the NMR spectra of the prepared Schiff base and its metal complexes are also reported. The nanocomplexes were characterized with a scanning electron microscope. The cytotoxicity of all newly synthesized compounds was demonstrated and they were tested for their activity against common pathogenic organisms and anticancer activity against human epithelial colorectal adenocarcinoma cells (Caco2). Some of the newly synthesized compounds had the best recorded anticancer activity against Caco2 cells. In addition, the three active compounds were tested for antibacterial activity. The three structures succeeded in affecting and stopping the growth of Klebsiella pneumoniae strain and the results revealed promising activity.