Synthesis of novel propargylated derivatives of noscapine using A3-coupling reaction and their anticancer properties

Abstract

A series of 21 novel compounds based on noscapine were synthesized and investigated as potential anticancer therapeutics. These new compounds were prepared from the N-demethylation of noscapine followed by the three-component A³-coupling of N-nornoscapine as a secondary amine, an aldehyde and a terminal alkyne catalyzed by copper iodide (CuI). Two classes of derivatives were synthesized by applying phenylacetylene and propargyl alcohol as the alkyne moiety. Chemical structures of the products were confirmed by ¹HNMR, ¹³CNMR, and HR-MS. In vitro cytotoxicity of the synthesized derivatives was studied on MCF-7 breast cancer cell line treated with different doses of compounds for 48 h. Compounds 6l, 6n and 6h (IC₅₀ = 18.94, 19.29 and 32.11 µM, respectively) displayed the highest potency compared to that of noscapine (IC₅₀ = 36.38 µM).