A comprehensive review of chemistry and pharmacological aspects of natural cyanobacterial azoline-based circular and linear oligopeptides

The cyanobacterial oligopeptides are recognized for being highly selective, efficacious and relatively safer compounds with diverse bioactivities. Azoline-based natural compounds consist of heterocycles which are reduced analogues of five-membered heterocyclic azoles. Among other varieties of azoline-based natural compounds, the heteropeptides bearing oxazoline or thiazoline heterocycles possess intrinsic structural properties with captivating pharmacological profiles, representing excellent templates for the design of novel therapeutics. The specificity of heteropeptides has been translated into prominent safety, tolerability, and efficacy profiles in humans. These peptidic congeners serve as ideal intermediary between small molecules and biopharmaceuticals based on their typically low production complexity compared to the protein-based biopharmaceuticals. The distinct bioproperties and unique structures render these heteropeptides one of the most promising lead compounds for drug discovery. The high degree of chemical diversity in cyanobacterial secondary metabolites may constitute a prolific source of new entities leading to the development of new pharmaceuticals. This review focuses on the azoline-based natural oligopeptides with emphasis on distinctive structural features, stereochemical aspects, biological activities, structure activity relationship, synthetic and biosynthetic aspects as well as mode of action of cyanobacteria-derived peptides. (c) 2021 Elsevier Masson SAS. All rights reserved.

Automated summary

Cyanobacterial oligopeptides are recognized for their diverse bioactivities and excellent pharmacological profiles, making them ideal templates for designing novel therapeutics. These heteropeptides exhibit prominent safety, tolerability, and efficacy in human drugs, serving as ideal intermediaries between small molecules and biopharmaceuticals. Their distinct bioproperties and unique structures make them one of the most promising lead compounds for drug discovery.