Article
Multidisciplinary Sciences
Zhouli Hu, Chenlong Wei, Qianqian Shi, Xianfang Hong, Jinhua Liu, Xiangui Zhou, Jinna Han, Wei Cao, Ashis Kumar Gupta, Xiaoxiang Zhang, Donghui Wei, Zhenqian Fu, Wei Huang
Summary: This paper describes a method for the asymmetric desymmetrization of amides using NHC organocatalysis, resulting in the generation of a diverse set of enantioenriched 4-amido esters with mild reaction conditions, wide substrate scope, and excellent atom economy.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Jaeki Min, Anand Mayasundari, Fatemeh Keramatnia, Barbara Jonchere, Seung Wook Yang, Jamie Jarusiewicz, Marisa Actis, Sourav Das, Brandon Young, Jake Slavish, Lei Yang, Yong Li, Xiang Fu, Shalandus H. Garrett, Mi-Kyung Yun, Zhenmei Li, Stanley Nithianantham, Sergio Chai, Taosheng Chen, Anang Shelat, Richard E. Lee, Gisele Nishiguchi, Stephen W. White, Martine F. Roussel, Patrick Ryan Potts, Marcus Fischer, Zoran Rankovic
Summary: IMiDs and IMiD-based PROTACs rapidly hydrolyze in commonly utilized cell media, affecting their efficacy; Novel CRBN binders, phenyl glutarimide (PG) analogues, were designed with high affinity and improved stability; Discovery of PG PROTAC 4c as a potent degrader of BET proteins, supporting the utility of PG derivatives in CRBN-directed PROTACs design.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Asmaa Abo Elgoud Said, Ahmed H. Afifi, Taha F. S. Ali, Mamdouh Nabil Samy, Usama Ramadan Abdelmohsen, Mostafa A. Fouad, Eman Zekry Attia
Summary: Chemical investigation of Aptenia cordifolia roots extract resulted in isolation and identification of eight known compounds. The basic ethyl acetate fraction showed high activity against HCV with an IC50 value of 2.4 mu g mL(-1), and some compounds exhibited strong binding to the active site of NS3/4A helicase.
Article
Pharmacology & Pharmacy
Ling Ma, Quanjie Li, Yongli Xie, Jianyuan Zhao, Dongrong Yi, Saisai Guo, Fei Guo, Jing Wang, Long Yang, Shan Cen
Summary: In this study, a cell-based assay for screening inhibitors against SARS-CoV-2 3CLpro was established using bioluminescence resonance energy transfer (BRET) technology. The assay was applied to screen a collection of known HIV/HCV protease inhibitors, and it was found that simeprevir showed the most potency against 3CLpro with the ability to bind to its active site pocket. This research demonstrates the feasibility of using the cell-based BRET assay for screening 3CLpro inhibitors and supports the potential of simeprevir for the development of such inhibitors.
ANTIVIRAL RESEARCH
(2022)
Article
Chemistry, Physical
Chen-Ji Huang, Hwei-Ling Peng, Anil Kumar Patel, Reeta Rani Singhania, Cheng-Di Dong, Chih-Yu Cheng
Summary: By designing a truncated NS3 protein, the expression and purification in E. coli were successfully improved, with fresh NS3 demonstrating higher specificity and antigenic activity. Long-term storage and thermal stability studies further confirmed the potential application value of fresh NS3 in HCV ELISA diagnosis.
Review
Chemistry, Organic
Yulia A. Trukhanova, Nikita M. Chernov, Elena V. Kuvaeva, Igor P. Yakovlev
Summary: Six-membered heterocyclic systems, such as glutarimides, are widely used in medicinal chemistry due to their wide range of bioactivity. The synthesis of C,N-highly functionalized glutarimides is an important topic in modern organic synthesis as it allows for the construction of more complex systems and expands the range of various drugs. This review discusses approaches to the synthesis of N- and C-functionally-substituted glutarimides presented in the literature from 2005 to 2022, including the enantioselective synthesis of spiroglutarimides, the use of organocatalysis in glutarimide synthesis, and optimization of the synthesis of known pharmaceuticals.
SYNTHESIS-STUTTGART
(2023)
Article
Biochemistry & Molecular Biology
Jun Lin, Li-Yuan Yang, Zhi-Di Pan
Summary: This study aimed to isolate bioactive compounds from the fermentation products of Aspergillus terreus that can inhibit NS3 protease of hepatitis C virus (HCV). The compounds were isolated using various chromatography techniques and their structures were determined through spectroscopic analysis. Two small molecule compounds were identified, including a new benzaldehyde and a compound obtained from microorganisms for the first time. Both compounds showed inhibitory activity against HCV NS3 protease. This study provides a new option for the development of anti-HCV drugs.
CHEMISTRY & BIODIVERSITY
(2023)
Article
Chemistry, Medicinal
Anjela Manandhar, Benjamin E. Blass, Dennis J. Colussi, Imane Almi, Magid Abou-Gharbia, Michael L. Klein, Khaled M. Elokely
Summary: The global population is currently facing a COVID-19 pandemic caused by SARS-CoV-2, with researchers exploring potential vaccines and treatments. The proteinase M3CLpro is being studied as a promising drug target, with investigations into its dynamic changes upon ligand binding using X-ray crystal structures. This research aims to aid in the design of potent protease inhibitors to combat the ongoing pandemic.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Review
Health Care Sciences & Services
JiHyun An, Dong Ah Park, Min Jung Ko, Sang Bong Ahn, Jeong-Ju Yoo, Dae Won Jun, Sun Young Yim
Summary: DAA therapy has shown safety and efficacy in patients with decompensated cirrhosis. The SVR rate was 86%, with low rates of HCC occurrence and mortality. PI-based treatment demonstrated similar clinical outcomes and adverse events compared to non-PI-based DAA treatment in DC patients.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Chemistry, Organic
Victorino Vallejos Gonzalez, Joachim Podlech
Summary: This study found that sulfur groups in different sulfur compounds exhibit different behaviors during oxidation reactions, with some behaving independently and others influencing each other. The oxidation of conformationally constrained dithiane derivative also showed unique properties in the formation of different oxidation products. The exclusive formation of sulfones by permanganate is attributed to its special oxidation mechanism involving sulfur as both nucleophile and electrophilic moiety.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Mousumi Hazra, Ramesh Chandra Dubey
Summary: This study analyzes the molecular mechanism of drug resistance variants in the hepatitis C virus protease through in vitro studies, providing insights into the binding mechanism of inhibitors. The findings emphasize the importance of developing novel inhibitors to overcome drug resistance.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Jacqueto Zephyr, Desaboini Nageswara Rao, Sang V. Vo, Mina Henes, Klajdi Kosovrasti, Ashley N. Matthew, Adam K. Hedger, Jennifer Timm, Elise T. Chan, Akbar Ali, Nese Kurt Yilmaz, Celia A. Schiffer
Summary: Third generation Hepatitis C virus (HCV) NS3/4A protease inhibitors, glecaprevir and voxilaprevir, show high efficacy against various genotypes and resistant variants. The fluorine substitutions on these inhibitors contribute to their improved potency and resistance profile, allowing them to adapt to structural changes induced by specific substitutions. A multi-disciplinary approach involving inhibitor design, enzyme inhibition assays, co-crystallography, and structural analysis was used to study the interactions between fluorinated inhibitors and the target protein, providing valuable insights for avoiding drug resistance.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Medicinal
Qing Liu, Ying Wei, Yongjia Hao, Jian Yang, Bowen Pan, Xiaosheng Yang, Ying Zhou, Xia Wang
Summary: In vitro inhibitory activities of four types of Hederagenin derivatives against HIV-1 and HCV NS3/4A proteases were evaluated.
NATURAL PRODUCT COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Thitiya Boonma, Bodee Nutho, Nitchakan Darai, Thanyada Rungrotmongkol, Nadtanet Nunthaboot
Summary: A156T mutation in HCV NS3/4A serine protease leads to drug resistance, and the newly approved drugs paritaprevir and glecaprevir exhibit different resistance profiles against this mutation. Molecular dynamics simulations and binding free energy calculations reveal that the binding affinities of paritaprevir and glecaprevir to A156T NS3/4A are significantly reduced compared to their wild-type complexes. The main contributions for the higher resistance of glecaprevir are the weak interactions with specific amino acids in NS3 protein and destabilized protein binding surface.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Armiya Sultana, Rafat Alib, Romana Ishratb, Sher Alic
Summary: The COVID-19 pandemic is caused by SARS-CoV-2, and the enzyme main protease (M-pro) is emerging as an attractive drug target. Through structure-assisted drug repositioning, saquinavir has been identified as a potent inhibitor of SARS-CoV-2 M-pro.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)