Emerging antimicrobial resistance has highlighted the need to design more effective antibiotics to treat deadly bacterial infections. Acinetobacter baumannii's outer membrane protein A (OmpA) is a critical virulence component involved in biofilm formation, immunomodulation, and antibiotic resistance, which characterizes it as a potential therapeutic target. The present study aimed to screen the natural product database (>1,00,000) to identify the potential inhibitor against OmpA. Molecular docking studies revealed that 10 compounds had good docking scores (≤ -7 kcal/mol) compared to the reported inhibitor epiestriol (-3.079). Further, these 10 compounds were subjected to ADME analysis and MMGBSA analysis. Based on MMGBSA results, we selected 5 compounds [NP-1 (MolPort-039-337-117), NP-5(MolPort-019-932-973), NP-6 (MolPort-005-948-336), NP-8(MolPort-042-673-978) and NP-9(MolPort-042-673-766)] with high binding affinity. Molecular dynamics simulation found that NP-5, NP-8, and NP-9 were stable after analysing their RMSD, RMSF, the radius of gyration, and hydrogen interactions of complexes. Our study revealed that NP-5, NP-8, and NP-9 bind perfectly with OmpA and can act as its potential inhibitors. The results of this study imply that the identified inhibitors have the potential for further investigation.Communicated by Ramaswamy H. Sarma.

2024-05-01·Journal of Agricultural and Food Chemistry

Design and Synthesis of Mandelic Acid Derivatives for Suppression of Virulence via T3SS against Citrus Canker

Article

作者: Wu, Zhibing ; Cui, Zi-Ning ; Wang, Xin ; Xian, Jiaxin ; Wang, Boli ; Shi, Huabin ; Song, Aiting ; Siddique, Faisal ; Zhang, Yu-Qing

Citrus canker, a highly contagious bacterial disease caused by Xanthomonas citri subsp. citri (Xcc), poses a substantial threat to citrus crops, leading to serious reductions in fruit yield and economic losses. Most commonly used bactericides against Xcc lead to the rapid development of resistant subpopulations. Therefore, it is imperative to create novel drugs, such as type III secretion system (T3SS) inhibitors, that specifically target bacterial virulence factors rather than bacterial viability. In our study, we designed and synthesized a series of mandelic acid derivatives including 2-mercapto-1,3,4-thiazole. Seven substances were found to reduce the level of transcription of hpa1 without affecting bacterial viability. In vivo bioassays indicated that compound F9 significantly inhibited hypersensitive response and pathogenicity. RT-qPCR assays showed that compound F9 visibly suppressed the expression of Xcc T3SS-related genes as well as citrus canker susceptibility gene CsLOB1. Furthermore, the combination with compound F9 and quorum-quenching bacteria HN-8 can also obviously alleviate canker symptoms.

2022-04-13·ACS Applied Materials & Interfaces2区 · 材料科学

Putting Forward NUS-8-CO₂H/PIM-1 as a Mixed Matrix Membrane for CO₂ Capture

2区 · 材料科学

Article

作者: Ramsahye, Naseem A. ; Semino, Rocio ; Fan, Dong ; Maurin, Guillaume ; Ozcan, Aydin

Mixed matrix membranes (MMMs) composed of NUS-8 metal-organic framework (MOF) nanosheets dispersed into a polymer of intrinsic microporosity 1 (PIM-1) polymer matrix are known to be promising candidates for CO₂/N₂ separation because of a solubility-driven separation mechanism. In this work, we predict that a chemical functionalization of the organic linker of NUS-8 by a CO₂-philic function confers an even better separation performance to the resulting MMM. Our simulations revealed that the NUS-8-CO₂H/PIM-1 composite exhibits a 3-fold increase in CO₂/N₂ selectivity versus the NUS-8/PIM-1 analogue while achieving a high CO₂ permeability (6700 barrer). We demonstrated that this improved level of performance is due to an increase both in the total MOF/polymer interfacial pore volume and in the CO₂-affinity due to the chemical functionalization. These results suggest that an appropriate choice of chemical functionalization of a MOF is a promising strategy to improve gas separation performances for MMM composites that exhibit a solubility-driven separation mechanism.

100 项与 Nu-8 相关的药物交易

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