Macroalgae have been reported as an important source of halogenated aromatic secondary metabolites, being the majority of these derivatives isolated from red algae. Halophenols and haloindoles are the most common haloaryl secondary metabolites isolated from these marine organisms. Nevertheless, some halogenated aromatic sesquiterpenes and naphthalene derivatives have also been isolated.

Most of these secondary metabolites showed interesting biological activities, such as antitumor, antimicrobial, antidiabetic, and antioxidant. This review describes in a systematic way the distribution and natural occurrence of halogenated aromatic secondary metabolites from extracts of red, brown, and green algae, as well as biological activities reported for these compounds.

Marine macroalgae play an essential role in the marine environment

Marine macroalgae play an essential role in the marine environment for the production of oxygen and as a source of food for marine animals. Moreover, these organisms generate compounds and products utilized in many commercial fields, such as fertilizers, and help to obtain compounds with pharmaceutical, cosmetic, and industrial applications. This review provides an overview of the most relevant haloaryl secondary metabolites isolated from macroalgae, including their distribution and biological activities.

Nevertheless, further biochemical analyses on green and brown macroalgae in the future may also result in the discovery of new compounds from other clades. Most of these halogenated compounds are brominated with a diverse degree of halogenation, as well as some examples of secondary metabolites with chlorine and iodine being described.

The most abundant haloaryl derivatives are bromophenols, with most of them possessing at least one catechol group. The biological potential of the majority of haloaryl secondary metabolites has been exhaustively reported, as they are well known their antioxidant, antitumor, antimicrobial, and antidiabetic activities. Therefore, it is expected that some of these compounds may be used in the future in drug discovery.

Among the bioactive compounds, bromophenols are the most promising

Several cell and tissue cultures derived from marine macroalgae have been developed, not only to facilitate the study of secondary metabolites biosynthesis, but also to allow the manipulation and controlled production of these compounds. Other strategies may include the chemical synthesis of these or nature-inspired haloaryl compounds. Among the bioactive compounds, bromophenols possessing 2,3-dibromo-3,4-dihydroxy phenyl rings, such as BDDE (17) and BDDPM (85), are the most promising.

Although several studies about the biological potential of these macroalgae natural products have been described, some unique indoles and aromatic sesquiterpenes have not been explored concerning their biological potential. Therefore, it is expected that the future exploitation of these haloaryl derivatives may contribute to medicinal chemistry in the discovery of innovative bioactive compounds.