Marine Peptides: Potential Basic Structures for the Development of Hybrid Compounds as Multitarget Therapeutics for the Treatment of Multifactorial Diseases

Abstract

Marine-derived peptides display potent antihypertensive, antioxidant, analgesic and antimicrobial biological effects. Some of them have also been found to have anticancer activity via various mechanisms differing from those of continental organisms. This diversity of properties-together with the peptides' efficacy, which has been confirmed in several in vitro and in vivo studies-make these compounds attractive as functional ingredients in pharmacy, especially in regard to multitarget drugs known as hybrids. Given the possibilities offered by chimeric structures, it is expected that a hybridization strategy based on a marine-derived compound could result in a long-awaited success in the development of new effective compounds to combat a range of complex diseases. However, despite the fact that the biological activity of such new hybrids may exceed that of their parent compounds, there is still an urgent need to carefully determine their potential off-targets and thus possible clinically important side effects. Given the above, the aim of this paper is to provide information on compounds of marine origin with peptide structures and to verify the occurrence and usage of hybrid compounds built from these structures. Furthermore, the authors believe that information presented here will serve to increase public awareness of the new opportunities arising from the combination of hybridization strategies with marine molecules with known structures and biological properties, thereby accelerating the development of effective drug candidates.

Keywords: efficacy; hybrid; marine peptides; safety profile; tolerability.

Figure 1

Types of hybrid molecules according to that location of their structural pharmacophores (P) in the scaffold. Fused hybrids mean that two biologically distinct pharmacophores are directly linked by the functional group of each fragment. Merged hybrids have components that overlap each other (the merged pharmacophores usually have similar elements/sequences), resulting in a smaller and simpler molecule, while linked hybrids are molecules that are bridged by a spacer that can be enzymatically stable (e.g., alkyl chain, aryl fragments) or can be cleaved, such as ester and disulfide bonds.

Figure 2

Representative structures of natural and synthetic marine-based chimeras.

Figure 3

Molecular structure of compound 6, which combines the marine peptide N6 and the cell-penetrating peptide Tat11, and was designed by Li et al. [123].