Anticancer Acridones, Part 2-Acronycine-Type Derivatives Modified with 2,5-Dihydro-1,2,4-Triazine Moiety: Synthesis and In Vitro Evaluation

抗癌吖啶酮类化合物,第二部分——2,5-二氢-1,2,4-三嗪基团修饰的吖啶辛型衍生物:合成及体外评价

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Abstract

This manuscript presents the synthesis of eight novel noracronycine derivatives containing 1,2,4-triazine moiety and evaluates their anticancer activity in vitro. The obtained compounds exhibit activity in the micromolar range and show selectivity towards glioblastoma A172 and breast cancer Hs578T cells. Compounds incorporating a dihydrotriazine moiety demonstrate an enhanced anticancer profile when compared to a noracronycine derivative lacking a triazine substituent. Furthermore, introducing a pyridyl group into the triazine core increases selective cytotoxicity toward cancerous cells. The lead compound exhibits an IC(50) value of 3.4 μM for glioblastoma A172, with a selectivity index of 7.59. Mechanistic studies reveal that the obtained compounds slow down cell division, while no significant apoptosis was detected.

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