Double the Chemistry, Double the Fun: Structural Diversity and Biological Activity of Marine-Derived Diketopiperazine Dimers

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2019 Oct 2

PMID 31569621

Citations 16

Authors

Nelson G M Gomes

Renato B Pereira

Paula B Andrade

Patricia Valentao

Affiliations

Soon will be listed here.

Abstract

While several marine natural products bearing the 2,5-diketopiperazine ring have been reported to date, the unique chemistry of dimeric frameworks appears to remain neglected. Frequently reported from marine-derived strains of fungi, many naturally occurring diketopiperazine dimers have been shown to display a wide spectrum of pharmacological properties, particularly within the field of cancer and antimicrobial therapy. While their structures illustrate the unmatched power of marine biosynthetic machinery, often exhibiting unsymmetrical connections with rare linkage frameworks, enhanced binding ability to a variety of pharmacologically relevant receptors has been also witnessed. The existence of a bifunctional linker to anchor two substrates, resulting in a higher concentration of pharmacophores in proximity to recognition sites of several receptors involved in human diseases, portrays this group of metabolites as privileged lead structures for advanced pre-clinical and clinical studies. Despite the structural novelty of various marine diketopiperazine dimers and their relevant bioactive properties in several models of disease, to our knowledge, this attractive subclass of compounds is reviewed here for the first time.

Citing Articles

Exploring the Diverse Landscape of Fungal Cytochrome P450-Catalyzed Regio- and Stereoselective Dimerization of Diketopiperazines.

Ma C, Wang W, Zhang K, Zhang F, Chang Y, Sun C Adv Sci (Weinh). 2024; 11(26):e2310018.

PMID: 38687842 PMC: 11234459. DOI: 10.1002/advs.202310018.

Marine-Derived Leads as Anticancer Candidates by Disrupting Hypoxic Signaling through Hypoxia-Inducible Factors Inhibition.

Garcia M, Andrade P, Lefranc F, Gomes N Mar Drugs. 2024; 22(4).

PMID: 38667760 PMC: 11051506. DOI: 10.3390/md22040143.

Total synthesis of complex 2,5-diketopiperazine alkaloids.

Walker K, Loach R, Movassaghi M Alkaloids Chem Biol. 2023; 90:159-206.

PMID: 37716796 PMC: 10955524. DOI: 10.1016/bs.alkal.2023.06.002.

Prenylation of dimeric cyclo-L-Trp-L-Trp by the promiscuous cyclo-L-Trp-L-Ala prenyltransferase EchPT1.

Li W, Xie X, Liu J, Yu H, Li S Appl Microbiol Biotechnol. 2023; 107(22):6887-6895.

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(+)/(-)-Yanhusamides A-C, three pairs of unprecedented benzylisoquinoline-pyrrole hetero-dimeric alkaloid enantiomers from .

Wang L, Xia G, Xia H, Wei X, Wang Y, Lin S Acta Pharm Sin B. 2023; 13(2):754-764.

PMID: 36873186 PMC: 9979263. DOI: 10.1016/j.apsb.2022.10.025.

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