ORCID Profile
0000-0003-2461-4325
Current Organisations
The Hong Kong Polytechnic University
,
Anhui Medical University
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: MDPI AG
Date: 16-04-2021
DOI: 10.3390/PH14040371
Abstract: Oseltamivir represents one of the most successful neuraminidase (NA) inhibitors in the current anti-influenza therapy. The 150-cavity of NA was identified as an additional binding pocket, and novel NA inhibitors have been designed to occupy the 150-cavity based on the structure information of oseltamivir carboxylate (OC) in complex with NA. In this study, a series of C-5-NH2-acyl derivatives of OC containing the pyrazole moiety were synthesized. Several derivatives exhibited substantial inhibitory activity against NA. Moreover, in silico ADME evaluation indicated that the derivatives were drug-like with higher oral absorption rates and greater cell permeability than OC. Additionally, molecular docking studies revealed that the derivatives interacted with both the NA enzyme active site and 150-cavity as expected. The results provided useful information for further structural optimization of OC.
Publisher: MDPI AG
Date: 07-04-2022
DOI: 10.3390/IJMS23084085
Abstract: Streptococci are a family of bacterial species significantly affecting human health. In addition, environmental Streptococci represent one of the major causes of erse livestock diseases. Due to antimicrobial resistance, there is an urgent need for novel antimicrobial agent discovery against Streptococci. We discovered a class of benzoic acid derivatives named sigmacidins inhibiting the bacterial RNA polymerase-σ factor interaction and demonstrating excellent antimicrobial activity against Streptococci. In this work, a combinational computer approach was applied to gain insight into the structural basis and mechanism of action of sigmacidins as antimicrobials against Streptococcus pneumoniae. Both two- and three-dimensional quantitative structure-active relationships (2D and 3D QSAR) of sigmacidins displayed good predictive ability. Moreover, molecular docking and molecular dynamics simulation studies disclosed possible contacts between the inhibitors and the protein. The results obtained in this study provided understanding and new directions to the further optimizations of sigmacidins as novel antimicrobials.
Publisher: MDPI AG
Date: 11-02-2022
DOI: 10.3390/PATHOGENS11020237
Abstract: Characterized by the high morbidity and mortality and seasonal surge, the influenza virus (IV) remains a major public health challenge. Oseltamivir is commonly used as a first-line antiviral. As a neuraminidase inhibitor, it attenuates the penetration of viruses through the mucus on the respiratory tract and inhibits the release of virus progeny from infected cells. However, over the years, oseltamivir-resistant strains have been detected in the IV surveillance programs. Therefore, new antivirals that circumvent the resistant strains would be of great importance. In this study, two novel secondary amine derivatives of oseltamivir CUHK326 (6f) and CUHK392 (10i), which bear heteroaryl groups of M2-S31 proton channel inhibitors, were designed, synthesized and subjected to biological evaluation using plaque assay. Influenza A virus (A/Oklahoma/447/2008, H1N1), influenza B viruses (B/HongKong/CUHK33261/2012), an oseltamivir-resistant influenza A virus (A/HongKong/CUHK71923/2009, H1N1) and an oseltamivir-resistant influenza B virus (B/HongKong/CUHK33280/2012) were included in the antiviral effect assessment compared to oseltamivir carboxylate (OC). Both novel compounds significantly reduced the plaque size of seasonal IV A and B, and performed similarly to OC at their corresponding half-maximal inhibitory concentration (IC50). CUHK392 (10i) functioned more effectively than CUHK326 (6f). More importantly, these compounds showed an inhibitory effect on the oseltamivir-resistant strain under 10 nM with selective index (SI) of .
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.EJMECH.2019.111635
Abstract: The discovery of novel potent neuraminidase (NA) inhibitors remains an attractive approach for treating infectious diseases caused by influenza. In this study, we describe the design and synthesis of novel N-substituted oseltamivir derivatives for probing the 150-cavity which is nascent to the activity site of NA. NA inhibitory studies showed that new derivatives demonstrated the inhibitory activity with IC
Publisher: MDPI AG
Date: 25-12-2022
DOI: 10.3390/IJMS24010339
Abstract: Staphylococcus aureus is a common human commensal pathogen that causes a wide range of infectious diseases. Due to the generation of antimicrobial resistance, the pathogen becomes resistant to more and more antibiotics, resulting in methicillin-resistant S. aureus (MRSA) and even multidrug-resistant S. aureus (MDRSA), namely ‘superbugs’. This situation highlights the urgent need for novel antimicrobials. Bacterial transcription, which is responsible for bacterial RNA synthesis, is a valid but underutilized target for developing antimicrobials. Previously, we reported a novel class of antimicrobials, coined nusbiarylins, that inhibited bacterial transcription by interrupting the protein–protein interaction (PPI) between two transcription factors NusB and NusE. In this work, we developed a ligand-based workflow based on the chemical structures of nusbiarylins and their activity against S. aureus. The ligand-based models—including the pharmacophore model, 3D QSAR, AutoQSAR, and ADME/T calculation—were integrated and used in the following virtual screening of the ChemDiv PPI database. As a result, four compounds, including J098-0498, 1067-0401, M013-0558, and F186-026, were identified as potential antimicrobials against S. aureus, with predicted pMIC values ranging from 3.8 to 4.2. The docking study showed that these molecules bound to NusB tightly with the binding free energy ranging from −58 to −66 kcal/mol.
No related grants have been discovered for Jiqing YE.