Synthesis and cytotoxic activity of imidazo[1,2-a]-1,3,5-triazine analogues of 6-mercaptopurine.
A series of 2-substituted imidazo[1,2-a]-1,3,5-triazines with various aliphatic and aromatic amines has been prepared and characterized by IR,1H-NMR, and elemental analysis. The initial in-vitro cytotoxicity studies with five human cancer cell lines showed that all but one of the compounds are without cytotoxic activity. The one active compound, 2-(indolin-1-yl)-7,8-dihydroimidazo[1,2-a]-1,3,5-triazine-4(6H)-thione 12, was tested on 12 human cancer cell lines. Of these, two lines, RT-4 and MCF-7, were the most sensitive to the compound, with IC50 values of 6.98 microM and 8.43 microM, respectively. When compared with the reference anticancer drug 6-mercaptopurine, only the RT-4 urinary bladder and KYSE-70 oesophagus cancer cell lines were more sensitive to the new compound. The antimetabolite thioguanine was more cytotoxic than 12 for all common cell lines tested.
Saczewski
Franciszek
F
Department of Chemical Technology of Drugs, Medical University of Gdansk, Gdansk, Poland. saczew@amg.gda.pl
Maruszak
Magdalena
M
Bednarski
Patrick J
PJ
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D015122:Mercaptopurine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013866:Thioguanine / Q000494:pharmacology; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007093:Imidazoles; D014227:Triazines; D015122:Mercaptopurine; D013866:Thioguanine