A series of 2,3-dioxoindolin-N-phenylacetamide derivatives was evaluated for inhibitory activity against CDC25B and PTP1B enzymes. Most of the derivatives showed inhibitory activity against CDC25B (IC50 = 3.2-23.2 µg/mL) and PTP1B (IC50 = 2.9-21.4 µg/mL). Compound 2h showed the most inhibitory activity in vitro with IC50 values of 3.2 and 2.9 µg/mL against CDC25B and PTP1B, respectively, compared with the reference drugs Na3VO4 (IC50 = 2.7 µg/mL) and oleanolic acid (IC50 = 2.3 µg/mL). The results of selectivity experiments showed that the 2,3-dioxoindolin-N-phenylacetamide derivatives were selective inhibitors against CDC25B and PTP1B. Enzyme kinetic experiments demonstrated that compound 2h was a specific inhibitor with the typical characteristics of a mixed inhibitor. In cytotoxic activity assays compound 2h had potent activity against A549, HeLa, and HCT116 cell lines. In addition, compound 2h showed potent tumor inhibitory activity in a colo205 xenograft model in vivo.

Neste estudo, uma nova série de derivados de 4H-[1,2,4]triazina[3,4-a]ftalazin-4-ona substituídos em C-7 foi sintetizada como potenciais agentes anticonvulsivantes. Suas atividades anticonvulsivantes foram avaliadas pelo teste do eletrochoque máximo (MES), e suas neurotoxicidades, pelo teste 'rotarod' de neurotoxicidade. Os resultados farmacológicos mostraram que a 7-hexiloxi-4H-[1,2,4]triazina[3,4-a]ftalazin-4-ona, 4e, foi a mais potente, com dose efetiva (ED50) de 6,6 mg kg-1 e dose tóxica mediana (TD50) de 39,4 mg kg-1, proporcionando um índice de proteção (PI=TD50 /ED50) de 6,0.

In this study, a novel series of 7-substituted-4H-[1,2,4]triazino[3,4-a]phthalazin-4-one derivatives was synthesized as potential anticonvulsant agents. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test, and their neurotoxicities were evaluated by the rotarod neurotoxicity test. The pharmacological results showed that 7-hexyloxy-4H-[1,2,4]triazino[3,4-a]phthalazin-4-one 4e was the most potent with median effective dose (ED50) value of 6.6 mg kg-1, median toxicity dose (TD50) of 39.4 mg kg-1, providing a protective index (PI=TD50 /ED50) value of 6.0.