A Facile Synthesis of Novel Isatinspirooxazine Derivatives and Potential in vitro Anti-Proliferative Activity

posted on 16.01.2019 by Iara S. Santos, Fabiana S. Guerra, Lucas F. Bernardino, Patrícia D. Fernandes, Lidilhone Hamerski, Bárbara V. Silva

Novel isatinspirooxazine derivatives were designed and synthesized as potential anti-proliferative agents. The new compounds were obtained from aldol condensation reactions between isatin and 3-(hydroxyimino)butan-2-one in the presence of an organic base in order to generate an aldol adduct, followed by cyclization in trifluoroacetic acid, providing the desired isatinspirooxazines in 30 to 80% yield. All the synthesized compounds, including the starting material and the synthetic intermediates, were tested for in vitro anti-proliferative activity against cell lines MCF-7 and MDA-MB231 (breast cancer) and A549 (lung cancer), highlighting the compound 4-methyl,5'-methyl-spiro[(5-aza-4-eno-3-one-cyclohexane)-1,3'-(1H-indol-one)] with an IC50 (half maximal inhibitory concentration) = 0.34 µM, more potent than the reference drug, doxorubicin (IC50 = 1.88 µM), in breast cancer line MDA-MB231.