Synthesis and biochemical evaluation of 2-amino-3-(7-methoxybenzo[d][1,3]dioxol-5-yl)propanoic acid

Heterocyclic 1,3-benzodioxole derivatives are interesting compounds due to their wide range of
pharmacological properties.[1] LASSBio 294 (1), for instance, is an alternative therapeutic for
cardiac dysfunction that increases the contractility of intact and saponin-skinned cardiac muscle
of Wistar rats,[2] whereas brasiliamide D (2) and its derivatives display convulsive activity.[3]
Analysis of the structure of brasiliamides suggests that they derive from two phenylpropanoic
amino acids, phenylalanine and 2-amino-3-(7-methoxybenzo[d][1,3]dioxol-5-yl)propanoic acid
(4), and it was suggested that the activity of the brasiliamide family was in part due to the 3-
methoxy-4,5-methylene dioxybenzyl group. So, we became interested in the potential biological
activity of this amino acid combining a benzodioxole moiety and an amino acid. The synthesis of 4 started from cheap and readily available vanillin (3) using well-established
procedures. We then investigated the antioxidant and antiproliferative activity of 4 and some
selected precursors. In the DPPH test, 4 showed the highest antiradical activity with IC50 value
of 80.91 μM. The enzymatic HRP/H2O2/L012 chemiluminescence assay also revealed a very
good antioxidant activity for all compounds with the best activity for 4 (IC50 = 0.36 μM). Cellular tests indicated that most of the tested compounds caused ROS inhibition without cell death.