A new antibacterial dioxopiperazine, dehydroxybisdethiobis(methylthio)gliotoxin (1), and the previously described bisdethiobis(methylthio)gliotoxin (2) and gliotoxin (3), have been isolated from the broth of a marine-derived fungus of the genus Pseudallescheria. The structure and absolute stereochemistry of the new compound was assigned on the basis of NMR and CD experiments. Compounds 1 to approximately 3 exhibit potent antibacterial activity against the methicillin-resistant and multidrug-resistant Staphylococcus aureus with MIC values of 31.2, 31.2, and 1.0 microg/ml, respectively. Compound 3 also exhibited a significant radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) with IC50 value of 5.2 microM.
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http://dx.doi.org/10.1038/ja.2006.35 | DOI Listing |
ACS Infect Dis
April 2024
Department of Biochemistry and Molecular Biology, University of South Alabama, Mobile, Alabama 36688, United States.
Effective treatment of gonorrhea is threatened by the increasing prevalence of strains resistant to the extended-spectrum cephalosporins (ESCs). Recently, we demonstrated the promise of the third-generation cephalosporin cefoperazone as an antigonococcal agent due to its rapid second-order rate of acylation against penicillin-binding protein 2 (PBP2) from the ESC-resistant strain H041 and robust antimicrobial activity against H041. Noting the presence of a ureido moiety in cefoperazone, we evaluated a subset of structurally similar ureido β-lactams, including piperacillin, azlocillin, and mezlocillin, for activity against PBP2 from H041 using biochemical and structural analyses.
View Article and Find Full Text PDFAlkaloids Chem Biol
September 2023
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, United States. Electronic address:
The 2,5-diketopiperazine (DKP) motif is present in many biologically relevant, complex natural products. The cyclodipeptide substructure offers structural rigidity and stability to proteolysis that makes these compounds promising candidates for medical applications. Due to their fascinating molecular architecture, synthetic organic chemists have focused significant effort on the total synthesis of these compounds.
View Article and Find Full Text PDFMolecules
September 2022
China State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Frontiers Science Center for New Organic Matter, Nankai University, Tianjin 300071, China.
Based on the scaffolds widely used in drug design, a series of novel tryptophan derivatives containing 2,5-diketopiperazine and acyl hydrazine moieties have been designed, synthesized, characterized, and evaluated for their biological activities. The bioassay results showed that the target compounds possessed moderate to good antiviral activities against tobacco mosaic virus (TMV), among which compounds , , , , and showed higher inactivation, curative, and protection activities in vivo than that of ribavirin (39 ± 1, 37 ± 1, 39 ± 1 at 500 mg/L) and comparable to that of ningnanmycin (58 ± 1, 55 ± 1, 57 ± 1% at 500 mg/L). Thus, these compounds are a promising candidate for anti-TMV development.
View Article and Find Full Text PDFChembiochem
February 2023
Institut für Pharmazeutische Biologie und Biotechnologie, Fachbereich Pharmazie, Philipps-Universität Marburg, Robert-Koch-Straße 4, 35037, Marburg, Germany.
Secondary metabolites derived from microorganism constitute an important part of natural products. Mining of the microbial genomes revealed a large number of uncharacterized biosynthetic gene clusters, indicating their greater potential to synthetize specialized or secondary metabolites (SMs) than identified by classic fermentation and isolation approaches. Various bioinformatics tools have been developed to analyze and identify such gene clusters, thus accelerating significantly the mining process.
View Article and Find Full Text PDFCurr Med Chem
March 2023
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China.
Background: 2,5-Diketopiperazines (DKPs), also called cyclic dipeptides, are the simplest peptide derivatives in nature that are formed by the condensation of two amino acids. They are an important category of bioactive substances with various structures.
Objective: This review focuses on the natural sources, synthetic processes, biological properties and MS fragmentation regularity of simple DKPs, in order to provide a reference for exploring future scientific and therapeutic potentials of these compounds.
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