Synthesis and Cytotoxic Activities of a Curcumin Analogue and Its bis- Mannich Derivatives
Kadir Ozden Yerdelen,
Halise Inci Gul,
Mannich bases (2-6) of curcumin analogue 1, [1,5-bis(4-hydroxy-phenyl)penta-1,4-dien-3-
one], were synthesized.Their cytotoxicity against human HL-60 promyelocytic leukemia and HSC-2,
HSC-3, and HSC-4 oral squamous carcinoma cell lines, as well as against normal oral cells was evaluated.
Mannich bases 2-5 displayed more potent cytotoxicity than curcumin and curcumin analogue 1
towards malignant cells with high PSE values (93.7-136.6). PARP1 cleavage assay demonstrated the
induction of apoptosis of HSC-2 cells by the most potent and tumor selective compound 4, which is a bis Mannich base
having N-methyl piperazine moieties. The results obtained suggest that preparation of Mannich bases of a curcumin analogue
1 was a useful chemical modification for cytotoxicity and tumour-selectivity for the compounds synthesized, and
apoptosis can be one of the possible mechanisms of action for the cytotoxicity.
Keywords: Anticancer, cytotoxicity, mannich bases, PARP1, PSE, SI.
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