Article
Biochemistry & Molecular Biology
Semih Yagci, Mahmut Gozelle, Selen Gozde Kaya, Yesim Ozkan, Ahmet Bugra Aksel, Filiz Bakar-Ates, Yasemin Dundar, Gokcen Eren
Summary: The study focused on hit-to-lead optimization of a potential SIRT1/2 inhibitor, resulting in improved selectivity for SIRT1 and SIRT2 inhibition. The structural modifications also influenced the cytotoxicity of the compounds against MCF-7 human breast cancer cell line, indicating the impact of SIRT1/2 inhibition on cancer cell viability.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Agriculture, Multidisciplinary
Cong Zhou, Xujuan Sun, Wen Fu, Zhong Li, Jiagao Cheng, Peter Maienfisch
Summary: A novel class of succinate dehydrogenase inhibitor (SDHI) fungicides, difluoromethyl-pyrazole beta-ketonitrile derivatives, were designed and evaluated for their antifungal activities. These compounds showed outstanding in vitro activity against Sclerotinia sclerotiorum and Rhizoctonia solani. Compound A14 exhibited significant inhibitory effect against porcine heart SDH and showed potential in the management of rice sheath blight. Molecular docking study and CoMSIA models provided insights into the binding and optimization strategies of these compounds.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Agriculture, Multidisciplinary
Ge Wei, Ming-Wei Huang, Wen-Jie Wang, Yuan Wu, Shu-Fen Mei, Li-Ming Zhou, Long-Can Mei, Xiao-Lei Zhu, Guang-Fu Yang
Summary: The carbon-silicon switch strategy has been effectively utilized to synthesize novel SDH inhibitors with enhanced fungicidal activity. The resulting compounds showed promising potential in disease control experiments and may serve as candidate fungicides in the future.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Xin Wen, Xinyuan Wu, Rui Jin, Xiaojie Lu
Summary: It is well known that heterocyclic compounds play a key role in improving drug activity, target selectivity, physicochemical properties as well as reducing toxicity. In this review, we summarized the representative heterocyclic structures involved in hit compounds which were obtained from DNA-encoded library from 2013 to 2021. The state of the art in heterocycle-based DEL synthesis and hit-to-lead optimization are highlighted in some examples. We hope that more and more novel heterocycle-based DEL toolboxes and in-depth pharmaceutical research on these lead compounds can be developed to accelerate the discovery of new drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Dan Liu, Ling Luo, Zhengxing Wang, Xiaoyun Ma, Xiuhai Gan
Summary: Plant diseases caused by fungi and nematodes have become increasingly serious. To address this issue, a series of novel derivatives with excellent antifungal and nematicidal activities were designed and synthesized, providing a potential solution for the joint control of these pathogens.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
D. Sala, H. Batebi, K. Ledwitch, P. W. Hildebrand, J. Meiler
Summary: The use of deep machine learning in protein structure prediction allows easy access to annotated conformations, which can compensate for missing experimental structures in structure-based drug discovery. However, the accuracy of these predicted conformations for screening chemical compounds that effectively interact with protein targets is still uncertain. This opinion article examines the benefits and limitations of using state-annotated conformations for ultra-large library screening, particularly for common drug targets like G-protein-coupled receptors.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Petko Alov, Hristo Stoimenov, Iglika Lessigiarska, Tania Pencheva, Nikolay T. Tzvetkov, Ilza Pajeva, Ivanka Tsakovska
Summary: This study screened over 650,000 compounds using in silico approaches to identify potential multi-target-directed ligand drugs for neurodegenerative diseases. Two hit compounds were obtained through subsequent evaluation and simulation, providing a rational basis for further development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Plant Sciences
Bingxue Sun, Rongjia Zhou, Guangxue Zhu, Xuewen Xie, Ali Chai, Lei Li, Tengfei Fan, Jingjing Shi, Baoju Li, Yanxia Shi
Summary: Cucumber leaf spot (CLS), caused by Corynespora cassiicola, is a serious disease in cucumber greenhouse cultivation. Resistance to succinate dehydrogenase inhibitors (SDHIs) due to point mutations in the SDHB/C/D gene has been reported. Different mutations result in different resistance levels, which vary over time and regions. We established allele-specific PCR (AS-PCR) and multiplex allele-specific PCR (MAS-PCR) assays for mutation detection and targeted control of CLS.
Article
Chemistry, Medicinal
Veronika Temml, Jakub Kollar, Theresa Schoenleitner, Anna Hoell, Daniela Schuster, Zsofia Kutil
Summary: In this study, structure- and ligand-based pharmacophore models were used for virtual screening of the SPECS compound library to discover novel GCPII-specific inhibitors. Six hits with moderate to high inhibitory potency were found, and the best virtual hit, a modified xanthene, inhibited GCPII with an IC50 value of 353 +/- 24 nM. This research demonstrates the applicability of pharmacophore-based modeling for the discovery of GCPII-specific inhibitors.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Christopher A. Reiher, David P. Schuman, Nicholas Simmons, Scott E. Wolkenberg
Summary: DNA-encoded library (DEL) screens are a powerful tool for hit-finding in biological targets, and studies have shown that the molecular property changes post-DEL screening are similar to those in hit-to-lead optimization following high throughput screens. Unique aspects of DEL, such as combinatorial synthetic methods and linker effects at the DNA attachment point, impact the strategies and outcomes of hit-to-lead optimizations.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Zeynab Fakhar, Leila Hejazi, Sayyed Abbas Tabatabai, Orde Q. Munro
Summary: The study explored novel compounds targeting sEH enzyme through computational investigations, identifying four best candidates from quinazoline-4(3H)-one derivatives as potential small molecule inhibitors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Jiamei Zhu, Jin Li, Dicheng Ma, Yangyang Gao, Jiagao Cheng, Wei Mu, Beixing Li, Feng Liu
Summary: This study reveals the variation in sensitivity of Corynespora cassiicola, the causal agent of Corynespora leaf spot, to succinate dehydrogenase inhibitors (SDHIs). Amino acid mutations in the sdhB/C/D genes of resistant strains affect the activity and binding features of SDH, resulting in multiple resistance levels and complex cross-resistance patterns to different SDHIs. This research provides a significant foundation for the development of efficient chemical control and integrated management strategies for Corynespora leaf spot.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2022)
Article
Endocrinology & Metabolism
Linyu Ran, Song Zhang, Guosheng Wang, Pei Zhao, Jiaxing Sun, Jiaqi Zhou, Haiyun Gan, Ryounghoon Jeon, Qiang Li, Joerg Herrmann, Feilong Wang
Summary: Glycolysis is essential for macrophage activation, but the involvement of glycolytic pathway metabolites in this process is not fully understood. Previous studies suggested the importance of the mitochondrial pyruvate carrier (MPC) in M1 activation, but using genetic approaches, this study shows that MPC is dispensable for M1 macrophage activation. The MPC inhibitor UK5099 inhibits inflammatory responses in M1 macrophages independent of MPC expression.
Article
Biochemistry & Molecular Biology
Muhammad Shahab, Muhammad Danial, Taimur Khan, Chaoqun Liang, Xiuyuan Duan, Daixi Wang, Hanzi Gao, Guojun Zheng
Summary: This study aims to identify strong compounds that can block the Anthranilate-CoA ligase enzyme produced by the pqsA gene, thereby inhibiting the quorum signaling system of P. aeruginosa. Virtual screening and molecular docking were conducted to identify potential lead compounds, which were further validated through molecular dynamic simulation. The selected compounds exhibited high binding affinity to the pqsA enzyme and interaction with the catalytic dyad, suggesting their potential as candidates for further research.
Article
Environmental Sciences
Alexandre Brenet, Rahma Hassan-Abdi, Nadia Soussi-Yanicostas
Summary: SDHIs, widely used fungicides in agriculture, have been found to potentially pose health risks by inhibiting not only fungal activity but also human cell activity. Recent study shows that bixafen, a new-generation SDHI, exhibits neurotoxicity in vertebrates, causing developmental defects in the central nervous system.