Guanidine Derivatives Containing the Chalcone Skeleton Are Potent Antiproliferative Compounds against Human Leukemia...

Area of Science:

• Medicinal Chemistry
• Cancer Biology
• Pharmacology

Background:

• The development of novel anti-cancer agents is crucial for improving patient outcomes.
• Guanidine derivatives represent a promising class of compounds with potential therapeutic applications.
• Targeting specific cancer cell lines, including leukemia and melanoma, remains a key challenge in oncology.

Purpose of the Study:

• To synthesize and evaluate the cytotoxic effects of eleven novel synthetic guanidines based on the 1,3-diphenylpropenone core.
• To identify specific guanidine compounds with potent anti-cancer activity against various human cancer cell lines.
• To assess the selectivity of these compounds towards cancer cells versus normal human cells.

Main Methods:

• Synthesis of eleven 1,3-diphenylpropenone-based guanidine derivatives.
• In vitro cytotoxicity assays against six human cancer cell lines (leukemia and melanoma).
• Evaluation of compound selectivity by testing against human peripheral blood mononuclear cells.

Main Results:

• Compound 6f, featuring a N-tosyl and N-methylpiperazine moiety, exhibited significant cytotoxicity against leukemia (U-937, HL-60, MOLT-3, NALM-6) and melanoma (SK-MEL-1) cells.
• Compound 6f showed low cytotoxicity against normal human peripheral blood mononuclear cells.
• Both compounds 6f and 6i induced apoptosis in leukemia cells via caspase-9 and caspase-3 activation and cytochrome c release.

Conclusions:

• Synthetic guanidines, particularly compound 6f, demonstrate potent and selective anti-cancer activity against leukemia and melanoma.
• These compounds induce programmed cell death (apoptosis) through well-defined molecular pathways.
• The identified guanidine derivatives hold promise for the development of new anti-cancer therapeutic strategies.