New Cytotoxic α‐Aminoacylamide and bis‐1,5‐Disubstituted Tetrazole Adducts From Amino‐Diterpene Molecules by Ugi Reaction

Abstract

In search for new molecules of diterpene origin with promising anticancer activity, two amino‐derivatives (methyl maleopimarate aminoimide and methyl 1β,13‐epoxydihydroquinopimarate C4‐hydrazone) were involved in the 4‐component Ugi reaction (Ugi‐4CR) and pseudo‐7‐component azido‐Ugi condensation (azido‐Ugi‐7CR) to afford a series of adducts holding α‐aminoacylamide and bis‐1,5‐disubstituted tetrazole substituents. The NCI‐60 cancer cell panel screening revealed diterpene‐type Ugi adducts 2, 5, and 6 with strong antiproliferative potency with GI50 in range of 1.2–15.4 μM. The high positive correlations with standard anticancer drugs suggest microtubules or progesterone and androgen receptors as possible targets of the synthesized compounds.