2. Academic Validation
  3. Discovery of β-carboline-(phenylsulfonyl)furoxan hybrids as potential anti-breast cancer agents

Discovery of β-carboline-(phenylsulfonyl)furoxan hybrids as potential anti-breast cancer agents

  • Bioorg Med Chem Lett. 2021 May 15:40:127952. doi: 10.1016/j.bmcl.2021.127952.
Xu Hu 1,  Xiang Gao 1,  Gang Gao 1,  Yanbing Wang 2,  Hao Cao 3,  Dahong Li 4,  Huiming Hua 5
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
  • 2 School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
  • 3 School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address: caohao2008@163.com.
  • 4 Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address: lidahong0203@163.com.
  • 5 Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address: huimhua@163.com.
PMID: 33744443 DOI: 10.1016/j.bmcl.2021.127952
Abstract

The cytotoxicity properties of the β-carboline Alkaloids have been broadly investigated. However, the potential application of β-carbolines was hindered due to the moderate activity in Cancer. In the present study, thirty β-carboline-(phenylsulfonyl)furoxan hybrids (11a-j, 12a-j and 13a-j) were designed and synthesized through esterification and amidation reaction strategy, and their inhibitory activities against the human breast Cancer cell lines MCF-7 and MDA-MB-231 were evaluated by CCK-8 assay. Biological evaluation presented that the most promising amide derivative 13h, substituted with p-methoxyphenyl group at position 1, generated high concentration of NO and evidently depressed the MCF-7 (IC50 = 0.89 μM) and MDA-MB-231 (IC50 = 0.62 μM) cells proliferation. Particularly, the wound healing and transwell assays demonstrated that 13h significantly inhibited the migration and invasion of MDA-MB-231cells. Furthermore, the preliminary mechanisms studies indicated that 13h induced G2/M phase arrest and Apoptosis possibly causing by ROS accumulation and ROS-mediated DNA damage. Based on these considerations, 13h may be a promising antimetastatic agent for breast Cancer, which is noteworthy for further exploration.

Keywords

Breast cancer; Migration apoptosis; NO donor; β-Carboline.

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