β-Nitrostyrene derivatives as broad range potential antifungal agents targeting fungal cell wall

Ramzan, Asiya; Padder, Sajad Ahmad; Masoodi, Khalid Z.; Shafi, Syed; Tahir, Inayatullah; Rehman, Reiaz Ul; Prasad, Rajendra; Shah, Abdul Haseeb

doi:10.1016/j.ejmech.2022.114609

Cited by 6 publications

(3 citation statements)

References 58 publications

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“…Following the manufacturer's protocol, transcriptomic mRNA libraries were prepared using NEB (cat# E7770L kit) as previously described [44]. The libraries were subjected to quantification using Qubit and Bioanalyser from Agilent.…”

Section: Transcriptomic Analysis To Study the Gene Expression In C El...mentioning

confidence: 99%

Snake venom-inspired novel peptides protectCaenorhabditis elegansagainst paraquat-induced Parkinson’s pathology

Madhubala,

Saikia,

Patra

et al. 2024

Preprint

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Thein vivoprotective mechanisms of two low molecular mass (∼1.4 kDa) novel custom peptides (CPs) against paraquat (PT)-induced neurodegenerative dysfunction in theCaenorhabditis elegansmodel were deciphered. CPs prevent the PT binding to the nerve ring adjacent to the pharynx inC. elegans(N2 strain) by stable and high-affinity binding to the tyrosine-protein kinase receptor CAM-1, resulting in significant inhibition of PT-induced toxicity by reducing enhanced reactive oxygen species production, mitochondrial membrane depolarization, and chemosensory dysfunction. The CPs inhibited PT-induced dopaminergic (DAergic) neuron degeneration and alpha-synuclein aggregation, the hallmarks of Parkinson’s Disease, in transgenic BZ555 and NL5901 strains ofC. elegans. The transcriptomic, functional proteomics, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses show that CPs prevented the increased expression of the genes involved in the skn-1 downstream pathway, thereby restoring PT-mediated oxidative stress, apoptosis, and neuronal damage inC.elegans. The CPs ability to repair PT-induced damage was demonstrated by a network of gene expression profiles illustrating the molecular relationships between the regulatory proteins. Further, CPs (10 mg/kg, parental route) did not show toxicity or induce inflammatory mediators in the mouse model.

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Section: Transcriptomic Analysis To Study the Gene Expression In C El...mentioning

confidence: 99%

Snake venom-inspired novel peptides protectCaenorhabditis elegansagainst paraquat-induced Parkinson’s pathology

Madhubala,

Saikia,

Patra

et al. 2024

Preprint

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“…AMPs exert their broad antimicrobial activity primarily by targeting structures such as pathogenic cell membranes, cell walls, biofilm formation, and hyphal formation, as well as influencing pathogenic factors [ 30 ]. Pathogenic cells differ from human cells, enabling selective targeting [ 31 , 32 , 33 ]. For example, plectasin inhibits the lipid II precursor in bacterial walls, demonstrating activity against Staphylococcus aureus without affecting human cells [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight

Ran,

Shehzadi,

Liang

et al. 2024

IJMS

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Soybean phytophthora blight is a severe menace to global agriculture, causing annual losses surpassing USD 1 billion. Present crop loss mitigation strategies primarily rely on chemical pesticides and disease-resistant breeding, frequently surpassed by the pathogens’ quick adaptive evolution. In this urgent scenario, our research delves into innovative antimicrobial peptides characterized by low drug resistance and environmental friendliness. Inhibiting chitin synthase gene activity in Phytophthora sojae impairs vital functions such as growth and sporulation, presenting an effective method to reduce its pathogenic impact. In our study, we screened 16 previously tested peptides to evaluate their antimicrobial effects against Phytophthora using structure-guided drug design, which involves molecular docking, saturation mutagenesis, molecular dynamics, and toxicity prediction. The in silico analysis identified AMP_04 with potential inhibitory activity against Phytophthora sojae’s chitin synthase. Through three rounds of saturation mutagenesis, we pin-pointed the most effective triple mutant, TP (D10K, G11I, S14L). Molecular dynamic simulations revealed TP’s stability in the chitin synthase-TP complex and its transmembrane mechanism, employing an all-atom force field. Our findings demonstrate the efficacy of TP in occupying the substrate-binding pocket and translocation catalytic channel. Effective inhibition of the chitin synthase enzyme can be achieved. Specifically, the triple mutant demonstrates enhanced antimicrobial potency and decreased toxicity relative to the wild-type AMP_04, utilizing a mechanism akin to the barrel-stave model during membrane translocation. Collectively, our study provides a new strategy that could be used as a potent antimicrobial agent in combatting soybean blight, contributing to sustainable agricultural practices.

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“…The reactions involving nitrostyrene compounds in recent years are summarized, and the reaction are divided into denitrification reactions and carbon-carbon double bonds according to reaction sites, expecting to provide a reference for new reactions with β-nitrostyrene compounds as substrates. Keywords β-nitrostyrene; denitrogenation reaction; carbon carbon double bond reaction β-硝基苯乙烯是重要的有机化合物, 广泛存在于具有多种生物活性的化合物结构和药物分子中, 其本身也具有抑制人端粒酶 [1] 、杀菌 [2][3] 及抗肿瘤 [4][5] 等活性. 近年来, 其在有机合成方向的应用也越来越被重视.…”

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confidence: 99%

Research Progress on Reactions Involving β-Nitrostyrene

Li,

Sun,

Zhao

et al. 2023

Chinese Journal of Organic Chemistry

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β-Nitrostyrene has a variety of biological activities and is also an important intermediate in organic synthesis, which can participate in a variety of chemical reactions due to its active chemical properties, and has attracted extensive attention from researchers. The reactions involving nitrostyrene compounds in recent years are summarized, and the reaction are divided into denitrification reactions and carbon-carbon double bonds according to reaction sites, expecting to provide a reference for new reactions with β-nitrostyrene compounds as substrates. Keywords β-nitrostyrene; denitrogenation reaction; carbon carbon double bond reaction β-硝基苯乙烯是重要的有机化合物, 广泛存在于具有多种生物活性的化合物结构和药物分子中, 其本身也具有抑制人端粒酶 [1] 、杀菌 [2][3] 及抗肿瘤 [4][5] 等活性. 近年来, 其在有机合成方向的应用也越来越被重视.

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β-Nitrostyrene derivatives as broad range potential antifungal agents targeting fungal cell wall

Cited by 6 publications

References 58 publications

Snake venom-inspired novel peptides protectCaenorhabditis elegansagainst paraquat-induced Parkinson’s pathology

Snake venom-inspired novel peptides protectCaenorhabditis elegansagainst paraquat-induced Parkinson’s pathology

Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight

Research Progress on Reactions Involving β-Nitrostyrene

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