Bioactivity-Guided Subtraction of MIQOX for Easily Available Isoquinoline Hydrazides as Novel Antifungal Candidates

Yang, Chen; Sun, Shengxin; Li, Wei; Mao, Yushuai; Wang, Qiao; Duan, Yabing; Csuk, René; Li, Shengkun

doi:10.1021/acs.jafc.3c02096

Cited by 8 publications

(5 citation statements)

References 38 publications

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“…Furthermore, current research reveals that regardless of the inhibitor type, be it organic small molecules, peptides, or proteins, as well as the different target sites (histone deacetylase, succinate dehydrogenase, pyruvate kinase), inhibitors consistently exhibit a more pronounced inhibitory effect on spore germination rather than mycelium growth in B. cinerea . The results of this study are entirely consistent with the literature, suggesting that the observed variations in inhibition effects are not directly associated with the Chitinase target of the DBA inhibitor.…”

Section: Resultsmentioning

confidence: 99%

Dibenzylideneacetone Overcomes Botrytis cinerea Infection in Cherry Tomatoes by Inhibiting Chitinase Activity

Niu,

Wang,

Wang

et al. 2023

J. Agric. Food Chem.

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Chitinase, a crucial component of the fungal cell wall and septa, plays an important role in fungal germination by hydrolyzing chitin to provide carbon and energy for fungal growth and reproduction. In this study, we initially screened dibenzylideneacetone (DBA), a small molecule with inhibitory activity against Botrytis cinerea Chitinase, exhibiting an IC50 of 13.10 μg/mL. By constructing a three-dimensional (3D) model of the B. cinerea Chitinase and utilizing computational biology approaches, we found DBA bound to the active site pocket and formed strong π–π interactions and hydrophobic interactions with Chitinase, indicative of its competitive inhibitory mode. Site-directed mutagenesis also revealed that TRP-382, TRP-135, and ALA-215 were key amino acid residues involved in DBA binding. Subsequent antifungal assays showed that DBA had an MIC of 32 μg/mL against B. cinerea and EC50 values of 16.29 and 14.64 μg/mL in inhibiting mycelial growth and spore germination, respectively. Importantly, in vivo experiments demonstrated that DBA treatment significantly extended the shelf life of cherry tomatoes by 2-fold. Therefore, DBA represents a promising antifungal agent for fruit preservation applications.

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Section: Resultsmentioning

confidence: 99%

Dibenzylideneacetone Overcomes Botrytis cinerea Infection in Cherry Tomatoes by Inhibiting Chitinase Activity

Niu,

Wang,

Wang

et al. 2023

J. Agric. Food Chem.

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“…By using the mycelial growth inhibition method, , the effective concentration for 50% inhibition (EC 50 ) was calculated for the promising compounds (Table S5). The target compounds were dissolved in DMSO and added to PDA medium to give the desired concentrations.…”

Section: Materials and Methodsmentioning

confidence: 99%

Structures, Biosynthesis, and Bioactivity of Oligomycins from the Marine-Derived Streptomyces sp. FXY-T5

Feng,

Li,

et al. 2024

J. Agric. Food Chem.

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Oligomycins are potent antifungal and antitumor agents. Mass spectrometry (MS)-and nuclear magnetic resonance (NMR)-based metabolomic fingerprinting analysis of marine-derived actinomycetes in our in-house library provided an oligomycinproducing strain, Streptomyces sp. FXY-T5. Chemical investigation led to the discovery of five new oligomycins, 24-lumooligomycin B (1), 4-lumooligomycin B (2), 6-lumooligomycin B (3), 40-homooligomycin B (4), and 15-hydroxy-oligomycin B (5), together with seven biosynthetically related known derivatives. Their structures were assigned by MS, NMR, electronic circular dichroism (ECD), and single-crystal X-ray diffraction analyses. The biosynthesis pathway of oligomycins was first proposed based on the analysis of a type I modular polyketide synthase (PKS) system and targeted gene disruption. As expected, the isolated oligomycins showed significant antiagricultural fungal pathogen activity and antiproliferative properties from which the possible structure− activity relationships were first suggested. More importantly, oligomycins induced significant G1-phase cell cycle arrest on cancer cells and significantly attenuated their Cyclin D1 and PCNA expression through a β-catenin signaling pathway.

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“…We used the same method to prepare other required medications. In vivo antifungal activity was tested using reported methods [ 36 , 37 , 38 ].…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, Antifungal Activity, and 3D-QSAR Study of Novel Quinoxaline-2-Oxyacetate Hydrazide

Teng,

Li,

Fang

et al. 2024

Molecules

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Plant pathogenic fungi pose a major threat to global food security, ecosystem services, and human livelihoods. Effective and broad-spectrum fungicides are needed to combat these pathogens. In this study, a novel antifungal 2-oxyacetate hydrazide quinoxaline scaffold as a simple analogue was designed and synthesized. Their antifungal activities were evaluated against Botrytis cinerea (B. cinerea), Altemaria solani (A. solani), Gibberella zeae (G. zeae), Rhizoctonia solani (R. solani), Colletotrichum orbiculare (C. orbiculare), and Alternaria alternata (A. alternata). These results demonstrated that most compounds exhibited remarkable inhibitory activities and possessed better efficacy than ridylbacterin, such as compound 15 (EC50 = 0.87 μg/mL against G. zeae, EC50 = 1.01 μg/mL against C. orbiculare) and compound 1 (EC50 = 1.54 μg/mL against A. alternata, EC50 = 0.20 μg/mL against R. solani). The 3D-QSAR analysis of quinoxaline-2-oxyacetate hydrazide derivatives has provided new insights into the design and optimization of novel antifungal drug molecules based on quinoxaline.

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Bioactivity-Guided Subtraction of MIQOX for Easily Available Isoquinoline Hydrazides as Novel Antifungal Candidates

Cited by 8 publications

References 38 publications

Dibenzylideneacetone Overcomes Botrytis cinerea Infection in Cherry Tomatoes by Inhibiting Chitinase Activity

Dibenzylideneacetone Overcomes Botrytis cinerea Infection in Cherry Tomatoes by Inhibiting Chitinase Activity

Structures, Biosynthesis, and Bioactivity of Oligomycins from the Marine-Derived Streptomyces sp. FXY-T5

Design, Synthesis, Antifungal Activity, and 3D-QSAR Study of Novel Quinoxaline-2-Oxyacetate Hydrazide

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