2. Academic Validation
  3. Novel nitric oxide-releasing derivatives of pyranocarbazole as antitumor agents: Design, synthesis, biological evaluation, and nitric oxide release studies

Novel nitric oxide-releasing derivatives of pyranocarbazole as antitumor agents: Design, synthesis, biological evaluation, and nitric oxide release studies

  • Eur J Med Chem. 2022 Dec 15:244:114832. doi: 10.1016/j.ejmech.2022.114832.
Yingda Zang 1,  Lei Huang 1,  Xinyi Chen 1,  Chuangjun Li 1,  Jie Ma 1,  Xiaoguang Chen 1,  Dongming Zhang 2,  Fangfang Lai 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People's Republic of China.
  • 2 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People's Republic of China. Electronic address: zhangdm@imm.ac.cn.
  • 3 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People's Republic of China. Electronic address: laifangfang@imm.ac.cn.
PMID: 36270090 DOI: 10.1016/j.ejmech.2022.114832
Abstract

In this study, a series of novel furoxan-based nitric oxide (NO) releasing derivatives of pyranocarbazole Alkaloids were designed, synthesized, and biologically evaluated against human Cancer cell lines. The derivatives showed considerable antiproliferative activities (IC50 = 0.05-7.55 μM) and most compounds showed higher activity in MDA-MB-231 than H460 and HeLa. Especially, the most active derivative 7a (IC50 = 0.05 μM) against MDA-MB-231 was about 60 times stronger than lead compound, as well as equivalent to positive control taxol, and produced high levels of NO in MDA-MB-231. Furthermore, 7a could significantly inhibit the growth of MDA-MB-231 tumors in vivo with low toxicity and the PI3K/Akt signaling pathway. These results indicated that compound 7a could be a promising lead for further studies.

Keywords

Antitumor; NO releasing; pyranocarbazole alkaloids.

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