Tyrosine-Derived Novel Benzoxazine Active in a Rat Syngenic Mammary Tumor Model of Breast Cancer
| Autor: | Rabi Sankar Bhatta, Jyotsana Singh, Rituraj Konwar, Sarvesh Kumar Verma, Arpita Banerjee, Amit Kumar, Asha Ganesher, Deepak Kumar, Amit Kumar Jana, Gautam Panda, Ashok Kumar Sharma |
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| Rok vydání: | 2021 |
| Předmět: |
Mammary tumor
Cell cycle checkpoint Chemistry Cancer Mammary Neoplasms Experimental Cell Cycle Checkpoints medicine.disease Benzoxazines Rats Disease Models Animal Breast cancer In vivo Apoptosis Drug Discovery medicine Cancer research Molecular Medicine Syngenic Animals Humans Tyrosine Female Tamoxifen medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 64(21) |
| ISSN: | 1520-4804 |
| Popis: | 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, -CF3, and -F were well tolerated on R1 and R2 positions of ring A, and R2 as -CH2CH2N(CH2)4 (N-ethyl pyrrolidine) and -CH2CH2N(CH2)5 (N-ethyl piperidine) chains on ring D increased activities (Series B, Figure 3). 13d selected as a lead compound (IC50: 0.20 to 0.65 μM) induces apoptosis, cell cycle arrest, and loss of mitochondrial membrane potential in breast cancer cells. Compound 13d was formulated into 13d-f using cyclodextrin to improve its solubility for a pharmacokinetic, in vivo efficacy study. Both 13d and 13d-f 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 13d could be a potential lead for the treatment of breast cancer and hence deserve further in-depth studies. |
| Databáze: | OpenAIRE |
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