Novel Mannich Bases of α‐Mangostin Bearing Methoxyphenyl Moieties with Antioxidant and Membrane‐protective activity

Abstract

A series of novel Mannich bases containing (monomethoxy-, dimethoxy-or trimethoxy)phenyl substituent and morpholine fragment have been synthesized via C-4-monoaminomethylation of α-mangostin, a natural hydroxyxanthone. This modification has led to a considerable reduction in erythrotoxicity of natural xanthone while preserving its high antioxidant activity. All synthesized derivatives have demonstrated higher radical scavenging activity and total antioxidant activity compared to those of α-mangostin, several compounds have also shown higher efficacy in the test system with red blood cells. In the model of oxidative hemolysis of red blood cells induced by hydrogen peroxide and 2,2'-azobis(2-amidinopropane) dihydrochloride, a Mannich base containing 3,4,5trimethoxyphenyl substituent has been shown to have the highest membrane-protective and antioxidant activity.

A Review of the Synthesis and Biological Activity of Flavonoid Mannich Base Derivatives

“…[10,28] In this context, the Mannich reaction proves to be a versatile tool for introducing amines into organic molecules. [29,30] Amine functional groups are frequently found in natural products, and they augment their biological effectiveness by offering extra sites for electrophilic interactions with cellular components. Furthermore, the introduction of amines can initiate a cascading effect, leading to a heightened chemical sensitization.…”

“…Recent studies have highlighted the significance of nitrogen‐containing compounds, particularly those derived from natural products, in the development of important drug classes [10,28] . In this context, the Mannich reaction proves to be a versatile tool for introducing amines into organic molecules [29,30] . Amine functional groups are frequently found in natural products, and they augment their biological effectiveness by offering extra sites for electrophilic interactions with cellular components.…”