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

ID: ALA5131473

Journal: Eur J Med Chem

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

Authors: Liao LS, Tan LJ, Chen Y, Yang QY, Choudhary MI, Pan YM, Tang HT, Su GF, Liang H, Chen ZF.

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.

CiteXplore: 35092899

DOI: 10.1016/j.ejmech.2022.114141

Patent ID: ┄