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Novel Nitric Oxide-Releasing Derivatives of Pyranocarbazole as Antitumor Agents: Design, Synthesis, Biological Evaluation, and Nitric Oxide Release Studies

SSRN Electronic Journal
  • 2
    Citations
  • 215
    Usage
  • 0
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    2
    • Citation Indexes
      2
  • Usage
    215
    • Abstract Views
      190
    • Downloads
      25

Article Description

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.

Bibliographic Details

Yingda Zang; Lei Huang; Xinyi Chen; Chuangjun Li; Jie Ma; Xiaoguang Chen; Dongming Zhang; Fangfang Lai

Elsevier BV

pyranocarbazole alkaloids; NO releasing; Antitumor

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