M. M. Ghorab

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.

The utility of isothiocyanato thiophenes in the synthesis of thieno[2,3-d]pyrimidine derivatives as possible radioprotective and anticancer agents

The synthesis of novel thioureido derivatives 3, 8, and 10; biscompounds 7, 9, and 11; and tetracyclic compounds 5, 6, and 16 utilizing 5-isothiocyanato-3-methyl-thiophene-2,4-dicarboxylic acid diethyl ester 2 are reported. The structures of these compounds were confirmed by microanalyses and IR, 1H NMR, and mass spectroscopy. Preliminary biological studies of some of the synthesized compounds showed promising radioprotective and anticancer activities.

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.

Synthesis of Some New Thieno[2,3-b]pyridines, Pyrimidino[4′,5′:4,5]thieno[2,3-b]-pyridines, and 2,3-Dihydro-1,3,4-thiadiazoles

Thieno[2,3-b]pyridines were synthesized from 6-benzofuran-2-yl-4-phenyl-2-sulfanylpyridine-3-carbonitrile and each of chloro acetone, ethyl chloroacetate, ω -bromoacetophenone, and chloroacetonitrile. These compounds were conveniently converted into novel pyrido[4′,5′:4,5]thieno[3,2-d]pyrimidines. Also, 2,3-dihydro-1,3,4-thiadiazole was synthesized from hydrazonoyl halides and 2-benzofuran-2-yl-3-(phenylamino)-3-thioxopropanenitrile. The structures of the products have been elucidated by elemental analyses, spectral data studies, and alternative syntheses whenever possible. The newly synthesized compounds were tested towards microorganisms.

The Synthesis of Some New Sulfur Heterocyclic Compounds as Potential Radioprotective and Anticancer Agents

Some novel 5-subistituted amino-3-methylthiophene-2,4-dicarboxylic acid diethyl ester (3–6), 3,5-dimethyl-4-oxo-2-thioxo-1,2,3,4-tetra-hydro-thieno[2,3-d]pyrimi-dine (7), imidazothienopyrimidene (8), and 1,2,4-triazolo-thienopyrimidine (11) were synthesized via a reaction of the isothiocyanate 2 with different reagents. The identification of the new compounds was established by elemental analysis, and IR, 1H NMR, and mass spectral data. Some prepared compounds were tested for their radioprotective and anticancer activities. Compounds 7 and 16 showed significant activities against EAC cells, while compound 5 exhibited radioprotective activity.

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.

Reactions with Hydrazonoyl Halides 53:1 Synthesis and Antimicrobial Activity of Triazolino[4,3-a]pyrimidines and 5-Arylazothiazoles

6-(2-Naphtyl)-1-phenyl-4-3,5-disubstituted 4,3a-triazolino[4,3-a]pyrimidines, [2(1-(2-naphthyl)-5-substitued (1-pyrazolin-3-yl)-4-phenyl(thiazol-5-yl)phenyldiazine and 1-(2-aza-2-[4-phenyldiazenyl)-(1,3-thiazol-2-yl)]amino}vinyl)-naphthalene-2-ol were synthesized via reactions of hydrazonoyl halides with 4-(2-naphthyl)-6-substituted 3,4-dihydropyrimidine-2-thione, Amino(3-(2-naphthyl)-5-substituted pyrazolin-2-ylmethane-1-thione, and 2-hydroxynaphthalenecarbaldehyde-thiosemicarbazone. All structures of the newly synthesized compounds were elucidated by elemental analysis, spectral data, and alternative synthesis methods whenever possible. Some of the new compounds were tested towards bacteria. In general, all tested compounds were capable of highly inhibiting the growth of gram positive of bacteria and gram negative.

Anticancer Activity of Novel Thiophenes Containing a Biological Active Diphenylsulfone, Diazepin, Piperidine, Oxazepine, Acryladehyde and Sulfonamide Moieties

A variety of thiophene derivatives bearing diphenylsulfone 3,4, diazepines 5b, 6b, phenylamino 7, piperidine 8, benzylpiperidine 9, oxazepines 10b, 11b, acrylaldehydes 12-14 and benzeonesulfanamide 15 were synthesized. some newly synthesized compounds were evaluated for their in vitro cytotoxic activity against human tumor breast cancer cell lines. The tested compounds showed moderate to good cytotoxic activity and indeed, some of them were more potent than doxorubicin as a reference drug.

Antiproliferative activity of novel thiophene and thienopyrimidine derivatives.

A novel series of newly synthesized thiophene derivatives, ethyl-4,5-dimethyl-2-(3-(3,4,5-trimethoxyphenyl)thioureido)thiophene-3-carboxylate 3, ethyl-2-[(2-(dimethylamino)ethoxy)mercapto)methyleneamino)]-4,5-dimethyl-thiophene-3-carboxylate 9, thienopyrimidines 4, 7, 10-20, triazolothienopyrimidines 5, 6 were prepared and tested for their antiproliferative activity. The structures of the synthesized compounds were confirmed on the basis of elemental analysis, IR, (1)H-NMR, (13)C-NMR and mass spectral data. The results showed that the synthesized compounds were more active on breast cancer than on colon cancer cell lines and the most potent compounds in this study are compounds 3 and 13 which exerted remarkable activity against MDA-MB-231 (breast cancer) and HT-29 (colon cancer) cell lines with IC50 values (40.68, 49.22 μM) for compound 3 and (34.04, 45.62 μM) for compound 13. Also, compounds 4-6, 9 showed a moderate activity against breast cancer cell line, while compounds 15, 19 and 20 showed no activity.

Synthesis, in-vitro anticancer screening and radiosensitizing evaluation of some new N-(quinoxalin-2-yl)benzenesulfonamide derivatives.

The objective of this work is to synthesize and investigate the anticancer activity of a new series of sulfaquinoxaline derivatives by incorporating biologically active moieties (thiourethane, thiazole, imidazole, imidazopyrimidine, imidazopyrimido-pyrimidine, thienopyrimidine, benzopyrimidinone, benzothiazole, thiazole and pyridine moieties). All the newly synthesized compounds were evaluated for their in-vitro anticancer activity against human liver cell line (HEPG2). All the tested compounds showed comparable activity to that of the reference drug 5-fluorouracil (IC50=40 µM), and the most potent compounds were found to be compounds 4 and 17 (IC50=4.29 and 11.27 µM, respectively). On the other hand, the most potent compounds 4 and 17 were evaluated as radiosensitizing agents.