For Mo Acetazolamide Analogue Design, Synthesis And Anticancer Activity Study

In this paper, the development of novel antitumor drugs and tumor-activated prodrugs (TAP) were described concisely, and the structure-activity relationship (SAR) and the mechanism of imidazotetrazinones were reviewed. On the base of the characteristics and the physiochemical properties of novel antitumor drug temozolomide, seventeen temozolomide analogues were designed and synthesized, including eight 3-methyl-4-oxoimidazo[5,l-d][l,2,3,5]tetrazine-8-carboxylates (Ia-Ih) and nine 3-methyl-4-oxoimidazo[5,1-d][l,2,3,5]tetrazine-8-carboxamides (IIa-IIi). The structures of the novel compounds were identified by the application of IR, 1H-NMR, 13C-NMR and MS, and the structures of compounds Ib and IIa were elucidated. The stability of compound Ib and temozolomide in four buffer solutions (pH 6.5, pH 6.0, pH4.5, pH 3.6) were determined by HPLC on which the solubility of seventeen compounds in acetic acid-sodium acetate (pH 3.6) buffer was examined. In vitro antitumor tests results showed that compound IIa had inhibited the growth of seven human tumor cells PC-3, HCT-15, T47D, MDA-MB-231, DU145, HT29 and Lncap at 40g/mL, other compounds and temozolomide had weak effect on the seven human tumor cells, compounds Ia-If , IIf, IIg had moderate activity on HL-60 cell, further bioactivity study was in progress.