Tyrosine-Derived Novel Benzoxazine Active in a Rat Syngenic Mammary Tumor Model of Breast Cancer.

In continuing efforts of improving benzoxazepine derivatives as an anti-breast cancer agent, a new chemical entity, benzoxazine, was designed from scaffold morphing. Structure-activity relationship studies revealed that H, -OMe, -CF, and -F were well tolerated on R and R positions of ring , and R as -CHCHN(CH) (-ethyl pyrrolidine) and -CHCHN(CH) (-ethyl piperidine) chains on ring D increased activities (, Figure 3). selected as a lead compound (IC: 0.20 to 0.65 μM) induces apoptosis, cell cycle arrest, and loss of mitochondrial membrane potential in breast cancer cells. Compound was formulated into using cyclodextrin to improve its solubility for a pharmacokinetic, efficacy study. Both and regressed tumor growth at concentrations of 5 and 20 mg/kg better than tamoxifen without any mortality in a rat syngenic mammary tumor model. Collectively, our data suggest that tyrosine-derived novel benzoxazine could be a potential lead for the treatment of breast cancer and hence deserve further in-depth studies.