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Open AccessArticle

Synthesis, X-ray Structure, Hirshfeld, DFT Conformational, Cytotoxic, and Anti-Toxoplasma Studies of New Indole-Hydrazone Derivatives

by Eman M. Hassan, Saied M. Soliman, Esraa A. Moneer, Mohamed Hagar, Assem Barakat, Matti Haukka and Hanaa Rasheed

Int. J. Mol. Sci. 2023, 24(17), 13251; https://doi.org/10.3390/ijms241713251 - 26 Aug 2023

Cited by 10 | Viewed by 2316

Abstract

The hydrazones 3a–c, were synthesized from the reaction of indole-3-carbaldehyde and nicotinic acid hydrazide, isonicotinic acid hydrazide, and benzoic acid hydrazide, respectively. Their structures were confirmed using FTIR, ¹HNMR, and ¹³CNMR spectroscopic techniques. Exclusively, hydrazones 3b and 3c were confirmed using single crystal X-ray crystallography to exist in the Eanti form. With the aid of DFT calculations, the most stable configuration of the hydrazones 3a–c in gas phase and in nonpolar solvents (CCl₄ and cyclohexane) is the ESyn form. Interestingly, the DFT calculations indicated the extrastability of the EAnti in polar aprotic (DMSO) and polar protic (ethanol) solvents. Hirshfeld topology analysis revealed the importance of the N…H, O…H, H…C, and π…π intermolecular interactions in the molecular packing of the studied systems. Distribution of the atomic charges for the hydrazones 3a–c was presented. The hydrazones 3a–c showed a polar character where 3b has the highest polarity of 5.7234 Debye compared to the 3a (4.0533 Debye) and 3c (5.3099 Debye). Regarding the anti-toxoplasma activity, all the detected results verified that 3c had a powerful activity against chronic toxoplasma infection. Compound 3c showed a considerable significant reduction percent of cyst burden in brain homogenates of toxoplasma infected mice representing 49%. Full article

(This article belongs to the Collection Feature Papers in 'Physical Chemistry and Chemical Physics')

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22 pages, 3017 KB

Open AccessArticle

Cyclodepsipeptide Biosynthesis in Hypocreales Fungi and Sequence Divergence of The Non-Ribosomal Peptide Synthase Genes

by Monika Urbaniak, Agnieszka Waśkiewicz, Artur Trzebny, Grzegorz Koczyk and Łukasz Stępień

Pathogens 2020, 9(7), 552; https://doi.org/10.3390/pathogens9070552 - 9 Jul 2020

Cited by 18 | Viewed by 4148

Abstract

Fungi from the Hypocreales order synthesize a range of toxic non-ribosomal cyclic peptides with antimicrobial, insecticidal and cytotoxic activities. Entomopathogenic Beauveria, Isaria and Cordyceps as well as phytopathogenic Fusarium spp. are known producers of beauvericins (BEAs), beauvenniatins (BEAEs) or enniatins (ENNs). The compounds are synthesized by beauvericin/enniatin synthase (BEAS/ESYN1), which shows significant sequence divergence among Hypocreales members. We investigated ENN, BEA and BEAE production among entomopathogenic (Beauveria, Cordyceps, Isaria) and phytopathogenic (Fusarium) fungi; BEA and ENNs were quantified using an LC-MS/MS method. Phylogenetic analysis of partial sequences of putative BEAS/ESYN1 amplicons was also made. Nineteen fungal strains were identified based on sequence analysis of amplified ITS and tef-1α regions. BEA was produced by all investigated fungi, with F. proliferatum and F. concentricum being the most efficient producers. ENNs were synthesized mostly by F. acuminatum, F. avenaceum and C. confragosa. The phylogeny reconstruction suggests that ancestral BEA biosynthesis independently diverged into biosynthesis of other compounds. The divergent positioning of three Fusarium isolates raises the possibility of parallel acquisition of cyclic depsipeptide synthases in ancient complexes within Fusarium genus. Different fungi have independently evolved NRPS genes involved in depsipeptide biosynthesis, with functional adaptation towards biosynthesis of overlapping yet diversified metabolite profiles. Full article

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20 pages, 2886 KB

Open AccessArticle

Enniatin Production Influences Fusarium avenaceum Virulence on Potato Tubers, but not on Durum Wheat or Peas

by Anas Eranthodi, Danielle Schneiderman, Linda J. Harris, Thomas E. Witte, Amanda Sproule, Anne Hermans, David P. Overy, Syama Chatterton, Jiajun Liu, Tao Li, Dianevys González-Peña Fundora, Weiquan Zhao and Nora A. Foroud

Pathogens 2020, 9(2), 75; https://doi.org/10.3390/pathogens9020075 - 21 Jan 2020

Cited by 32 | Viewed by 5021

Abstract

Fusarium avenaceum is a generalist pathogen responsible for diseases in numerous crop species. The fungus produces a series of mycotoxins including the cyclohexadepsipeptide enniatins. Mycotoxins can be pathogenicity and virulence factors in various plant–pathogen interactions, and enniatins have been shown to influence aggressiveness on potato tubers. To determine the role of these mycotoxins in other F. avenaceum–host interactions, ENNIATIN SYNTHASE 1 (ESYN1) disruption and overexpression mutants were generated and their ability to infect wheat and peas investigated. As a preliminary study, the transformants were screened for their ability to cause potato tuber necrosis and, consistent with a previous report, enniatin production increased necrotic lesion size on the tubers. By contrast, when the same mutants were assessed in their ability to cause disease in pea roots or durum wheat spikes, no changes in disease symptoms or virulence were observed. While it is known that, at least in the case of wheat, exogenously applied enniatins can cause tissue necrosis, this group of mycotoxins does not appear to be a key factor on its own in disease development on peas or durum wheat. Full article

(This article belongs to the Special Issue Pathogenesis of Fungal and Bacterial Microbes)

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17 pages, 3348 KB

Open AccessArticle

Enniatin and Beauvericin Biosynthesis in Fusarium Species: Production Profiles and Structural Determinant Prediction

by Vania C. Liuzzi, Valentina Mirabelli, Maria Teresa Cimmarusti, Miriam Haidukowski, John F. Leslie, Antonio F. Logrieco, Rocco Caliandro, Francesca Fanelli and Giuseppina Mulè

Toxins 2017, 9(2), 45; https://doi.org/10.3390/toxins9020045 - 25 Jan 2017

Cited by 77 | Viewed by 9377

Abstract

Members of the fungal genus Fusarium can produce numerous secondary metabolites, including the nonribosomal mycotoxins beauvericin (BEA) and enniatins (ENNs). Both mycotoxins are synthesized by the multifunctional enzyme enniatin synthetase (ESYN1) that contains both peptide synthetase and S-adenosyl-l-methionine-dependent N-methyltransferase activities. Several Fusarium species can produce ENNs, BEA or both, but the mechanism(s) enabling these differential metabolic profiles is unknown. In this study, we analyzed the primary structure of ESYN1 by sequencing esyn1 transcripts from different Fusarium species. We measured ENNs and BEA production by ultra-performance liquid chromatography coupled with photodiode array and Acquity QDa mass detector (UPLC-PDA-QDa) analyses. We predicted protein structures, compared the predictions by multivariate analysis methods and found a striking correlation between BEA/ENN-producing profiles and ESYN1 three-dimensional structures. Structural differences in the β strand’s Asn789-Ala793 and His797-Asp802 portions of the amino acid adenylation domain can be used to distinguish BEA/ENN-producing Fusarium isolates from those that produce only ENN. Full article

(This article belongs to the Special Issue Selected papers from 1^st China Mycotoxin Conference: Current trends in mycotoxin prevention and control)

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19 pages, 705 KB

Open AccessArticle

Sequence Divergence of the Enniatin Synthase Gene in Relation to Production of Beauvericin and Enniatins in Fusarium Species

by Łukasz Stępień and Agnieszka Waśkiewicz

Toxins 2013, 5(3), 537-555; https://doi.org/10.3390/toxins5030537 - 13 Mar 2013

Cited by 51 | Viewed by 7988

Abstract

Beauvericin (BEA) and enniatins (ENNs) are cyclic peptide mycotoxins produced by a wide range of fungal species, including pathogenic Fusaria. Amounts of BEA and ENNs were quantified in individual rice cultures of 58 Fusarium strains belonging to 20 species, originating from different host plant species and different geographical localities. The species identification of all strains was done on the basis of the tef-1α gene sequence. The main aim of this study was to analyze the variability of the esyn1 gene encoding the enniatin synthase, the essential enzyme of this metabolic pathway, among the BEA- and ENNs-producing genotypes. The phylogenetic analysis based on the partial sequence of the esyn1 gene clearly discriminates species producing exclusively BEA from those synthesizing mainly enniatin analogues. Full article

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