2. Academic Validation
  3. One-pot synthesis of oxoaporphines as potent antitumor agents and investigation of their mechanisms of actions

One-pot synthesis of oxoaporphines as potent antitumor agents and investigation of their mechanisms of actions

  • Eur J Med Chem. 2022 Mar 5;231:114141. doi: 10.1016/j.ejmech.2022.114141.
Lan-Shan Liao 1,  Lin-Jie Tan 1,  Yin Chen 1,  Qi-Yuan Yang 1,  Muhammad Iqbal Choudhary 2,  Ying-Ming Pan 1,  Hai-Tao Tang 1,  Gui-Fa Su 3,  Hong Liang 4,  Zhen-Feng Chen 5
Affiliations

Affiliations

  • 1 State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, PR China.
  • 2 International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 74270, Pakistan.
  • 3 State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, PR China. Electronic address: [email protected].
  • 4 State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, PR China. Electronic address: [email protected].
  • 5 State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, PR China. Electronic address: [email protected].
PMID: 35092899 DOI: 10.1016/j.ejmech.2022.114141
Abstract

An efficient one-pot reaction for the synthesis of oxoaporphine Alkaloids has been developed. Twenty-three compounds of oxoaporphine Alkaloids were prepared and assessed for their antitumor activities. Most compounds inhibited the growth of T-24 tumor cells in vitro. Particularly, 4B displayed the most potent activity with an IC50 value of 0.5 μM, which was 19-fold more potent than the parent compound 4. The substitution at C3-position of oxoaporphine core by -NO2 significantly enhanced the Anticancer activity. Mechanism studies indicated that 4 and 4B induced cell cycle arrest at G2/M phase; in contrast, 4V induced cell cycle arrest at the S phase. Increase of mitochondrial ROS/Ca2+ and decrease of MMP, accompanied by activation of Caspase-3/9, were observed in T-24 cells after exposure to compounds 4, 4B and 4V, suggesting that the mitochondrial pathway was involved in the induced Apoptosis. Moreover, compound 4B effectively inhibited tumor growth in a mouse xenograft model bearing T-24.

Keywords

Antitumor activity; Apoptosis; Cell cycle; Oxoaporphine.

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