A series of diethylamine Mannich base of asymmetrical mono-carbonyl analogs of curcumin (AMACs) were synthesized and evaluated for cytotoxic activity against Hela Cell lines. The structures of the synthesized compounds were confirmed on the basis of FTIR, ¹H-NMR, ¹³C-NMR and mass spectral data. Preliminary cytotoxic test using BSLT showed that all the synthesized compounds exhibited more potent cytotoxic activity than that of curcumin. While results of MTT assay showed that all the synthesized compounds exhibited more potent antiproliferative activity against HeLa cell lines than that of cisplatin. Compound 2b exhibited as the most potent compound of the series. Compound 2a, 2b, 2c, and 2f had IC₅₀ (µM) less than that of compound 1a, 1b, 1c and 1f indicating that the addition of diethylamine Mannich base improves the antiproliferative activity of the parent compound.