Novel Chemotherapy Agents Show Promise in Cancer Treatment

Scientists at Duquesne University's Pharmaceutical Sciences Division have designed, synthesized, and evaluated two novel compounds that have shown promise in cancer treatment. These single agents, which combine antiangiogenic and cytotoxic effects, have been tested in a mouse model and have demonstrated significant tumor growth inhibition, inhibition of metastasis, and antiangiogenic effects. The compounds, which target vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor receptor-beta (PDGFR-beta), and human thymidylate synthase (hTS), have been found to be as effective as standard chemotherapy agents.

Key Takeaways:

• The novel compounds, substituted pyrimido[4,5-b]indoles, have been designed to inhibit VEGFR-2, PDGFR-beta, and hTS, making them potential single agents for cancer treatment.
• The compounds have been found to be as effective as standard chemotherapy agents in inhibiting tumor growth, metastasis, and angiogenesis in a COLO-205 xenograft mouse model.
• The compounds were synthesized through the nucleophilic displacement of the common intermediate 5-chloro-9H-pyrimido[4,5-b]indole-2,4-diamine with appropriate benzenethiols.
• The inhibitory potency of the compounds against VEGFR-2, PDGFR-beta, and hTS is better than or close to standards.
• The compounds have demonstrated potent tumor growth inhibition, inhibition of metastasis, and antiangiogenic effects in vivo.
• The study's authors conclude that the compounds afford combination chemotherapeutic potential in single agents.

Statistics:

• 76% tumor growth inhibition (TGI) at 35 mg/kg in the COLO-205 xenograft mouse model
• Significantly decreased liver metastases
• Potent antiangiogenic effects in vivo

Sources:

• Gangjee, A., et al. (2010). Single agents with designed combination chemotherapy potential: synthesis and evaluation of substituted pyrimido[4,5-b]indoles as receptor tyrosine kinase and thymidylate synthase inhibitors and as antitumor agents. Journal of Medicinal Chemistry, 53(4), 1563-1578.
• Enzyme Research
• Angiogenesis Weekly

Note: The study was published in Journal of Medicinal Chemistry in 2010 and reported in Angiogenesis Weekly in the same year.