Synthesis of Antifungal Heterocycle-Containing Mannich Bases: A Comprehensive Review

Abstract

Mannich bases are a class of organic compounds usually obtained by the condensation reaction between an amine, a compound with active hydrogens, and an aldehyde. They are versatile intermediates in organic synthesis, and those compounds containing this motif find applications in pharmaceutical, agrochemical, and even material fields since they are widely known for their wide range of biological activities, including antimicrobial properties. Thus, as part of our interest in antifungal agents, this narrative review aimed to gather information from the literature on the synthesis of various representative Mannich-base-containing compounds, particularly centered on those exhibiting antifungal properties. In this context, the compilation indicated that Mannich bases could be considered as a relevant toxophore/pharmacophore by incorporating heterocyclic moieties to be implemented for the design of new antifungal agents, given its proven efficacy against phytopathogens, other opportunistic human pathogens, and some dermatophytic fungal species, which can be further exploited as agrochemical agents or in medicinal applications to treat fungal infections. The antifungal effect exhibited by Mannich bases conjugated with oxa and/or aza-heterocycles suggests that compounds that have a heterocyclic system attached to the β-amino core are attractive alternatives oriented to the synthesis of novel and helpful antifungal agents.