Background:
Chemotherapy is one of the mainstays of cancer treatment, despite the serious
side effects of the clinically available anticancer drugs. In recent years increasing attention has
been directed towards novel agents with improved efficacy and selectivity. Compounds with chalcone
backbone have been reported to possess various biological activities such as anticancer, antimicrobial,
anti-inflammatory, analgesic, antioxidant, etc. It was reported that aminomethylation of
hydroxy chalcones to the corresponding Mannich bases increased their cytotoxicity. In this context,
our interest has been focused on the design and synthesis of the so-called multi-target molecules,
containing two or more pharmacophore fragments.
Methods:
A series of Mannich bases were synthesized by the reaction between 6-[3-(3,4,5-
trimethoxyphenyl)-2-propenoyl]-2(3Н)-benzoxazolone, formaldehyde, and a secondary amine. The
structures of the compounds were confirmed by elemental analysis, IR and NMR spectra. The new
Mannich bases were evaluated for their in vitro cytotoxicity against a panel of human tumor cell
lines, including BV-173, SKW-3, K-562, HL-60, HD-MY-Z and MDA-MB-231. The effects of selected
compounds on the cellular levels of glutathione (GSH) were determined.
Results:
The new compounds 4a-e exhibited concentration-dependent cytotoxic effects at micromolar
concentrations in MTT-dye reduction assay against a panel of human tumor cell lines, similar to those of
starting chalcone 3. The tested agents led to concentration - dependent depletion of cellular GSH levels,
whereby the effects of the chalcone prototype 3 and its Mannich base-derivatives were comparable.
Conclusion:
The highest chemosensitivity to the tested compounds was observed in BV-
173followed by SKW-3 and HL-60 cell lines.
