Natural Cyclopeptides as Anticancer Agents in the Last 20 Years

Abstract

Cyclopeptides or cyclic peptides are polypeptides formed by ring closing of terminal amino acids. A large number of natural cyclopeptides have been reported to be highly effective against different cancer cells, some of which are renowned for their clinical uses. Compared to linear peptides, cyclopeptides have absolute advantages of structural rigidity, biochemical stability, binding affinity as well as membrane permeability, which contribute greatly to their anticancer potency. Therefore, the discovery and development of natural cyclopeptides as anticancer agents remains attractive to academic researchers and pharmaceutical companies. Herein, we provide an overview of anticancer cyclopeptides that were discovered in the past 20 years. The present review mainly focuses on the anticancer efficacies, mechanisms of action and chemical structures of cyclopeptides with natural origins. Additionally, studies of the structure–activity relationship, total synthetic strategies as well as bioactivities of natural cyclopeptides are also included in this article. In conclusion, due to their characteristic structural features, natural cyclopeptides have great potential to be developed as anticancer agents. Indeed, they can also serve as excellent scaffolds for the synthesis of novel derivatives for combating cancerous pathologies.

Photoinduced Synthesis of Methylated Marine Cyclopeptide Galaxamide Analogs with Isoindolinone as Anticancer Agents

“…The restricted rotation of the C-N amide bond and constrained cyclic conformation also give the cyclopeptides strong rigidity, thus facilitating their binding to the target protein. Moreover, because of their medium molecular weights, small cyclic peptides have been recognized to be able to combine the advantages of small molecules (easy absorption) and polypeptides (high specificity), and with the great efforts of plant chemists and marine biologists, more and more biologically active natural cyclic peptides have been found, providing important resources for drug development [3,4].…”

Structural and Biofunctional Insights into the Cyclo(Pro-Pro-Phe-Phe-) Scaffold from Experimental and In Silico Studies: Melanoma and Beyond

“…According to our previous investigations, the Pro-Pro-Phe-Phe sequence in parent nonadeca cyclolinopeptide A (CLA) and its analogs play a pivotal role in bioactivity [25]. Moreover, proline has a significant impact on anticancer activity, and cyclic peptides containing aromatic amino acid residues possess extra rigidification of the backbone leading to increasing affinity to diverse targets [26,27]. Furthermore, synthetic amino acids such as β-homo amino acid residues can improve pharmacological properties, mainly bioactivity and stability, in vivo half-life, lipophilicity, potency, selectivity, and reduced toxicity [28].…”

In vitro Anticancer Potentialities of Three Egyptian Cyanobacterial Isolates against Breast Adenocarcinoma and Hepatocellular Carcinoma Cell Lines

“…Several cyanobacteria produce compounds, such as synthadotin, cryptophycin, and curacin, which are identified to have anticancer effect and include compounds that have effectively succeeded to enter clinical trials (Singh et al, 2011;Qamar et al, 2021). Cyanobacteria isolated from marine environments are being studied extensively because 50% of these organisms are regarded as a potential source of anticancer drugs, whereas organisms isolated from freshwater habitats and soil are poorly evaluated (Agatonovic-Kustrin et al, 2018;Zhang et al, 2021). Therefore, in the present investigation, we aimed to screen the anticancer activity of three cyanobacterial extracts isolated mainly from fresh to brackish water habitats against HCC (Hep-G2) and breast cancer adenocarcinoma (MCF-7) cell lines.…”