Synthesis and antitumor activity of some novel quinazoline derivatives bearing the biologically active thione moiety.
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.
Ghorab
Moustafa M
MM
Department of Drug Radiation Research, National Centre for Radiation Research and Technology, Nasr City, Cairo, Egypt. ghorabmoustafa@yahoo.com
El-Sayed Barakat
Saber
S
Saker
Helmy M
HM
Abd Rabo
Mahmoud M
MM
D000465:Algorithms; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004317:Doxorubicin / Q000627:therapeutic use; D007202:Indicators and Reagents; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013871:Thiones / Q000737:chemistry*
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D011799:Quinazolines; D013871:Thiones; D004317:Doxorubicin