Antitumor agent-61

Antitumor agent-61 (Compound 9b), Irinotecan (Ir) derivative, is a potential antitumor agent. Antitumor agent-61 displays potent activity with IC50s of 0.92, 1.39, 1.75, 2.20, 3.05 and 3.23 μM against five human cancer cells SK-OV-3, SK-OV-3/CDDP, U2OS, MCF-7, A549 and MG-63, respectively. Antitumor agent-61 induces SK-OV-3 cells apoptosis through mitochondrion pathways[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Antitumor agent-61 (compound 6b) shows anti-proliferation activity with IC50 values of 3.05, 2.20, 3.23, 1.75, 0.92 and 1.39 μM for A549, MCF-7, MG-63, U2OS, SK-OV-3 and SK-OV-3/CDDP cells[1]. Antitumor agent-61 (compound 6b) (50-150 μM) shows a certain inhibitory activity against Topo I at 150 μM[1]. Antitumor agent-61 (compound 6b) (5-10 μM; 24 hours, SK-OV-3 cells) induces apoptosis through mitochondrial pathway. Decrease the MMP level and increase ROS level in a dose-dependent manner [1]. Cell Cytotoxicity Assay[1] Cell Line: SK-OV-3 cells Concentration: 5.0 and 10 μM Incubation Time: 24 hours Result: Increased the percentage of apoptosis cells (including the early and late apoptosis) from 21.11% (5 μM) to 32.27% (10 μM), respectively and the apoptosis rate was significantly greater than that of Ir. Cell Cycle Analysis[1] Cell Line: SK-OV-3 cells Concentration: 5.0 and 10 μM Incubation Time: 24 hours Result: Increased the percentage of S stage in a dose-dependent manner. Western Blot Analysis[1] Cell Line: SK-OV-3 cells Concentration: 5.0 and 10 μM Incubation Time: 24 hours Result: Decreased the expression of antiapoptotic protein Bcl-2, while increased pro-apoptotic Bax and caspase expression.

Antitumor agent-61 (compound 6b) (10-20 mg/kg; i.h.; Twice daily, for 28 days; BALB/c nude mice with SK-OV-3 xenograft) reduces mean NPC tumor burden in a dose-dependent manner[1]. Animal Model: BALB/c nude mice with SK-OV-3 xenograft[1] Dosage: 10 and 20 mg/kg Administration: Subcutaneous injection; Twice daily, for 28 days. Result: Suppressed tumor growth by 47.7% and 56.8% for 10 and 20 mg/kg, respectively, without affecting body weight or causing any overt adverse effects.

[1]. Xiaochao Huang, et al. Synthesis, mechanisms of action, and toxicity of novel aminophosphonates derivatives conjugated irinotecan in vitro and in vivo as potent antitumor agents. Eur J Med Chem. 2020 Mar 1;189:112067.