Novel phenoxy-((phenylethynyl) selanyl) propan-2-ol derivatives as potential anticancer agents

Area of Science:

• Medicinal Chemistry
• Oncology
• Pharmacology

Background:

• Selenocompounds are recognized for their protective effects on healthy cells and their ability to induce apoptosis in tumor cells, making them promising candidates for cancer research.
• The synthesis and evaluation of novel organoselenium derivatives are crucial for developing new anti-cancer agents.

Purpose of the Study:

• To synthesize and evaluate the anti-proliferative activities of novel phenoxy-((phenylethynyl) selanyl) propan-2-ol derivatives against human cancer cell lines.
• To identify specific compounds with potent anti-tumor activity and elucidate their mechanism of action.

Main Methods:

• Synthesis of 23 novel phenoxy-((phenylethynyl) selanyl) propan-2-ol derivatives.
• In vitro anti-proliferation assays against human cancer cell lines.
• Flow cytometry to analyze cell cycle phase arrest and apoptosis induction.
• Western blot analysis to assess changes in cell cycle and apoptosis-related proteins.
• In vivo xenograft tumor experiments in nude mice and assessment of toxic effects.

Main Results:

• Most synthesized compounds exhibited significant anti-proliferative activity.
• Compounds 3h, 3g, and 3h-2, featuring halogen substituents, showed the most potent anti-tumor activity.
• Compounds 3h, 3g, and 3h-2 induced G2/M phase arrest and apoptosis in A549 cells.
• Compound 3h demonstrated in vivo antitumor effects in xenograft models without evident toxicity and alleviated cisplatin-induced organ damage.

Conclusions:

• Novel organoselenium compounds, particularly halogenated derivatives like 3h, exhibit potent anti-cancer properties.
• Compound 3h effectively induces apoptosis and inhibits tumor growth in vivo, suggesting its potential as a lead compound for cancer therapy.
• Compound 3h shows promise for cancer treatment with a favorable safety profile and protective effects against chemotherapy-induced organ damage.