ABSTRACT
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.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Pyrazoles/chemical synthesis , Pyrazoles/pharmacology , Animals , Carcinoma, Ehrlich Tumor/drug therapy , Carcinoma, Ehrlich Tumor/pathology , Cell Line, Tumor , Cell Survival/drug effects , Drug Design , Drug Screening Assays, Antitumor , Humans , Indicators and Reagents , Mass Spectrometry , Spectrophotometry, InfraredABSTRACT
The reactivity of isothiocyanate 1 towards some nitrogen nucleophils was investigated. Thus, interaction of 1 with p-flouroaniline, benzylamine, 2-aminopyridine, and 4-aminoantipyrine yielded the corresponding quinazoline derivatives 3-7, respectively. Triazolo-quinazoline 10 was obtained in good yield via reaction of isothiocyanate 1 with thiosemicarbazide. When the isothiocyanate 1 was reacted with 1,2-phenylenediamine and/or 2,3-diaminopyrimidine the quinazoline derivatives 12, 13 were obtained. The biscompounds 16, 17 and 18 were isolated on hot reaction of 1 with 1,3-phenylenediamine or 2,6-diamino-4-hydroxy pyrimidine and/or 1,4 phenylenediamine (2:1 mol), while the quinazoline derivative 19 was obtained from the filtrate of the reaction mixture of 18. Assay for antitumor activity showed that compound 7 has a significant activity against Ehrlich ascites carcinoma tumor cells (in vitro); the percent for the non-viable cells was about 100%, 100% and 95% (significant) at a concentration of 100, 50 and 25 microg/ml, respectively.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Quinazolines/chemical synthesis , Quinazolines/pharmacology , Thiones/chemistry , Algorithms , Animals , Antibiotics, Antineoplastic/therapeutic use , Antineoplastic Agents/chemistry , Carcinoma, Ehrlich Tumor/drug therapy , Cell Survival/drug effects , Chemical Phenomena , Chemistry, Physical , Doxorubicin/therapeutic use , Indicators and Reagents , Quinazolines/chemistryABSTRACT
The syntheses of novel 1,2,4-triazolothienopyrimidine derivatives (4a,b), thiourea derivatives (5-8) and biscompounds having a thieno[2,3-d]pyrimidine nucleus (13-16) utilizing the 2-isothiocyanato derivatives 2a,b are reported. The structures of these compounds were confirmed by microanalysis, IR, 1H-NMR and mass spectrometry. Preliminary biological studies of some synthesized compounds showed promising antitumor and radioprotective activities.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Pyrimidines/chemical synthesis , Pyrimidines/pharmacology , Radiation-Protective Agents/chemical synthesis , Radiation-Protective Agents/pharmacology , Sulfur Compounds/chemical synthesis , Sulfur Compounds/pharmacology , Animals , Antioxidants/metabolism , Carcinoma, Ehrlich Tumor/drug therapy , Female , Gamma Rays , Glutathione/blood , Indicators and Reagents , Lipid Peroxidation/drug effects , Lipid Peroxidation/radiation effects , Mice , Neoplasm Transplantation , Superoxide Dismutase/bloodABSTRACT
Several sulfonamides having pyrrole (5a-c, 8, 11b-19, 23, 24), pyrrolo[2,3-d] pyrimidine (6, 7, 10, 20, 21, 25) and pyrrolo[2,3-b]pyridine (22) were synthesized and evaluated for their antitumor and radioprotective activities. The structure of the synthesized compounds was elucidated by elemental analyses and spectral data. Compounds 5a, 16, 17, 19, and 23 displayed more potent antitumor activities than the reference drug, doxorubicin. On the other hand compounds 19, 23 and 25 exhibited radioprotective activities.
