Tryptophan derived natural marine alkaloids and synthetic derivatives as promising antimicrobial agents

Abstract

Antimicrobial resistance has become a major threat to public health worldwide, as pathogenic microorganisms are finding ways to evade all known antimicrobials. Therefore, the demand for new and effective antimicrobial agents is also increasing. Natural products have always played an important role in drug discovery, either by themselves or as inspiration for synthetic compounds. The marine environment is a rich source of bioactive metabolites, and among them, tryptophan-derived alkaloids stand out for their abundance and by displaying a variety of biological activities, with antimicrobial properties being among the most significant. This review aims to reveal the potential of marine alkaloids derived from tryptophan as antimicrobial agents. Relevant examples of these compounds and their synthetic analogues reported in the last decades are presented and discussed in detail, with their mechanism of action and synthetic approaches whenever relevant. Several tryptophan-derived marine alkaloids have shown potent and promising antimicrobial activities, whether against bacteria, fungi, or virus. Synthetic approaches to many of the compounds have been developed and recent methodologies are proving to be efficient. Even though most of the studies regarding the antimicrobial activity are still preliminary, this class of compounds has proven to be worth of further investigation and may provide useful lead compounds for the development of antimicrobial agents. Overall, marine alkaloids derived from tryptophan are revealed as a valuable class of antimicrobials and molecular modifications in order to reduce the toxicity of these compounds and additional studies regarding their mechanism of action are interesting topics to explore in the future.

Keywords: Antimicrobial; Indole; Marine alkaloids; Medicinal chemistry; Tryptophan.