Marine-Derived Macrolides 1990–2020: An Overview of Chemical and Biological Diversity

Abstract

Macrolides are a significant family of natural products with diverse structures and bioactivities. Considerable effort has been made in recent decades to isolate additional macrolides and characterize their chemical and bioactive properties. The majority of macrolides are obtained from marine organisms, including sponges, marine microorganisms and zooplankton, cnidarians, mollusks, red algae, bryozoans, and tunicates. Sponges, fungi and dinoflagellates are the main producers of macrolides. Marine macrolides possess a wide range of bioactive properties including cytotoxic, antibacterial, antifungal, antimitotic, antiviral, and other activities. Cytotoxicity is their most significant property, highlighting that marine macrolides still encompass many potential antitumor drug leads. This extensive review details the chemical and biological diversity of 505 macrolides derived from marine organisms which have been reported from 1990 to 2020.

Macrolides: From Toxins to Therapeutics

“…Increasing knowledge of the biochemistry of these compounds has explained a wide range of toxic effects, from quick paralysis to more gradual changes in target cells. Marine macrolide toxins have also been of interest due to their potential therapeutic properties against cancer and fungal or parasitic infections, and their ability to act as immunosuppressants [ 3 , 4 ]. Toxins produced by bacterial species, such as the mycolactones from Mycobacterium ulcerans , also have a wide range of effects on host cells, many of which have yet to be discovered [ 5 ].…”

“…Macrolide antibiotics are typically 12- to 16-membered macrolactone rings that contain various amino sugars and lack the acyclic side chain characteristic of macrolide toxins ( Table 2 ) [ 4 , 47 , 53 , 54 ]. For example, erythromycin, the first macrolide antibiotic to be discovered, is a 14-membered macrolide that has a wide antimicrobial spectrum [ 47 ].…”

“…Commonly prescribed macrolide antibiotics include azithromycin, erythromycin, and clarithromycin. These macrolides consist of a 14- or 15-membered alkylated lactone ring with hydroxyl groups on C3, C5, C6, C11, and C12 and a desosamine and decladinose sugar on C3 and C5 [ 4 , 47 , 55 ].…”

“…Many macrolides also exhibit toxic bioactivity, which may be a cause of the adverse side effects observed in response to the administration of macrolide drugs. Indeed, one of the largest classes of macrolides is toxins, many of which are produced from marine sources [ 4 ]. On the other hand, some macrolide mechanisms of toxicity have been manipulated for use in therapeutic applications.…”

“…Each subclass has been reviewed for structural similarities, mechanisms of action, pharmacology, and side effects in human beings. For a comprehensive review of macrolides from marine sources, see the review written by Zhang et al in 2021 [ 4 ].…”