Article
Biochemistry & Molecular Biology
Chengqian Wei, Junjie Huang, Yu Wang, Yifang Chen, Xin Luo, Shaobo Wang, Zengxue Wu, Jixiang Chen
Summary: A series of new oxadiazole sulfone derivatives containing an amide moiety were synthesized to screen high-efficiency antibacterial agents for rice bacterial diseases. Compound 10 showed excellent antibacterial activity against Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola, with EC50 values superior to commercial bactericides. Compound 10 demonstrated superior protective and curative activities against rice bacterial leaf blight and rice bacterial leaf streak compared to other tested compounds. Additionally, compound 10 exhibited potential mechanisms of action by affecting extracellular polysaccharides, cell membranes, and enzyme activity of dihydrolipoamide S-succinyltransferase to inhibit the growth of Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Xue-ping Hu, Liu Yang, Xin Chai, Yi-xuan Lei, Md Shah Alam, Lu Liu, Chao Shen, De-jun Jiang, Zhe Wang, Zhi-yong Liu, Lei Xu, Kang-lin Wan, Tian-yu Zhang, Yue-lan Yin, Dan Li, Dong-sheng Cao, Ting-jun Hou
Summary: This study utilized an integrated molecular modeling strategy to identify two lead compounds that could inhibit DprE1 and showed inhibitory activity against Mycobacterium tuberculosis in vitro, with low cytotoxicity against mouse embryo fibroblast NIH-3T3 cells. This research provides an effective strategy for discovering novel anti-TB lead compounds.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Tengyue Zhang, Siqi Xing, Jiyu Du, Jucheng Xia, Shuanghong Dong, Zeng Li, Zhicheng Liu, Yang Song
Summary: In this study, a receptor structure-based virtual screening strategy was developed to identify potential TLR/MD2 inhibitors for inflammatory diseases. Hit compound 94 exhibited promising anti-inflammatory activity and low toxicity, inhibiting the activation of TLR4/MD2-associated signaling pathways.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Meiling Shen, Lingfeng Li, Yue Li, Xi Gu, Longhui Bai, Chengfeng Xia, Wenyong Xiong, Zhili Zuo
Summary: This study conducted virtual screening of over 1.5 million molecules from the Chemdiv database to identify potential inhibitors of hTRPC5. The screening process evaluated the affinities of the candidates and assessed their inhibitory effects on Ca2+ influx. Two molecules, SML-1 and SML-13, showed significant inhibition of intracellular Ca2+ levels and could potentially be lead compounds for the development of therapeutics targeting hTRPC5 and its associated physiological activities and diseases.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Dongyan Gu, Mengmeng Zhang, Lvtao Cai, Chang Wang, Yu -Bo Zhou, Jia Li, Rong Sheng
Summary: Compound 1 with pyrazolo[1,5-a]quinoxalin-4(5H)-one scaffold was identified as a hit for inhibiting PI3K alpha activity through virtual screening. Structural modifications based on similarity search and molecular docking yielded a novel series of pyrazolo[1,5-a]quinoxalin-4(5H)-one derivatives. The most potent compound 49b exhibited improved PI3K alpha inhibitory activity with good isoform selectivity and demonstrated promising pharmacokinetic properties. Further development of compound 49b as a potential PI3Ka inhibitor is warranted.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Gaia Pasqualetto, Marika Zuanon, Andrea Brancale, Mark T. Young
Summary: The ATP-gated ion channels P2X4 and P2X7 receptors are drug targets for inflammatory pain. Through virtual screening, a compound (GP-25) was found to display antagonist activity at human P2X7 but not at human P2X4. Further screening led to the discovery of five additional compounds with antagonist activity at human P2X7. Docking experiments revealed the structural basis for the lack of activity of GP-25 at human P2X4.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Huizhen Ge, Lizeng Peng, Zhou Sun, Huanxiang Liu, Yulin Shen, Xiaojun Yao
Summary: In this study, novel HPK1 inhibitors were identified using virtual screening and kinase inhibition assays. Molecular dynamics simulations were performed to analyze the interaction between the identified compounds and HPK1 kinase domain. The most potent compound showed potential for further development as an HPK1 inhibitor for immunotherapy.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Automation & Control Systems
Yue Zhao, Rui-fang Chen, Zhen-Ke Deng, Liu-Xia Zhang, Yan Cheng, Alex F. Chen, Dong-Sheng Cao
Summary: RSK2 plays a critical role in cell proliferation and anticancer therapy as a potential target. Virtual screening identified compounds with potential anticancer activity.
CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS
(2021)
Article
Agriculture, Multidisciplinary
Tao Chen, Wen-Qin Li, Zheng Liu, Wen Jiang, Tian Liu, Qing Yang, Xiao-Lei Zhu, Guang-Fu Yang
Summary: The study demonstrates that compounds with a biphenyl-sulfonamide skeleton have great potential as OfHex1 inhibitors, showing higher potency than some reported nonglycosyl-based inhibitors. These compounds were found to be competitive inhibitors with respect substrate and exhibited potent drug properties, indicating their potential value in pest management.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Muya Xiong, Tianqing Nie, Qiang Shao, Minjun Li, Haixia Su, Yechun Xu
Summary: This study identified three potential covalent non-peptidomimetic inhibitors for the treatment of the coronavirus based on virtual screening. The effectiveness of one compound was validated through enzymatic activity assay and crystal structure analysis. The study also demonstrated an effective computational approach for seeking new covalent small molecules.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Xu Lian, Zhonghua Xia, Xueyao Li, Pavel Karpov, Hongwei Jin, Igor Tetko, Jie Xia, Song Wu
Summary: This study compiled a dataset of 2,3-diaminoquinoxalines, identified a new antibacterial agent, and discovered two new GyrB inhibitors with potential for further development, through chemical synthesis, cheminformatics modeling, and virtual screening.
BIOORGANIC CHEMISTRY
(2021)
Article
Biology
Hajar Sirous, Giuseppe Campiani, Vincenzo Calderone, Simone Brogi
Summary: HDAC inhibitors have shown potential in reversing cancer-associated epigenetic changes, but the non-selective profile of current inhibitors limits their clinical utility, leading to the search for isoform-selective inhibitors. This study focused on virtual screening for HDAC1 inhibitors, identifying novel benzamide-based analogs with potential inhibitory activity. The computational approach presented in this study offers guidelines for the development of improved benzamide-based derivatives targeting HDAC1 isoform.
COMPUTERS IN BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Shih-Chung Yen, Liang-Chieh Chen, Han-Li Huang, Wei-Chun HuangFu, Yi-Ying Chen, Ssu-Ting Lien, Hui-Ju Tseng, Tzu-Ying Sung, Jui-Hua Hsieh, Wei-Jan Huang, Shiow-Lin Pan, Kai-Cheng Hsu, Tony Eight Lin
Summary: A dual inhibitor, K783-0308, targeting FLT3 and MNK2, was identified in this study. It showed inhibitory effects on both FLT3 and MNK2, as well as promising results in suppressing AML cell growth and inducing cell cycle arrest.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Xin-Yu Leng, Shuang Gao, Yi-Fan Ma, Li-Xia Zhao, Meng Wang, Fei Ye, Ying Fu
Summary: This study generated two pharmacophore models for virtual screening of HPPD inhibitors and successfully identified four compounds with high energy, good solubility, and safety properties. Three novel HPPD inhibitors were designed and synthesized, one of which demonstrated similar inhibition and herbicidal activity as mesotrione, with better crop safety. The properties of these compounds were found to be superior to mesotrione, making them potential candidates for novel HPPD inhibitor herbicides.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lihong Yang, Mukuo Wang, Beibei Li, Shangqin Xu, Jianping Lin
Summary: In this study, potent inhibitors for CDK2 were identified through a multistage virtual screening strategy and bioassay validations. Compound 1 (C1) showed better biochemical activity compared to other selected compounds, as validated by ADP-Glo Kinase assay. Cell viability assay demonstrated that C1 had a minimum inhibition concentration lower than 4 μM for CDK2. Further functional tests revealed significant antiproliferative, pro-apoptosis, and anti-migration activity of C1 in melanoma cell lines (A375 cells, WM35 cells, and A875 cells). The findings suggest that C1, screened from compound libraries, could be developed as an effective therapeutic agent for melanoma treatment.
Article
Biochemistry & Molecular Biology
Ankit Uniyal, Manoj Kumar Mahapatra, Vinod Tiwari, Rajat Sandhir, Rajnish Kumar
Summary: The COVID-19 pandemic has created a healthcare crisis worldwide. The recent discovery of the crystallized structure of the main protease (M-pro) from SARS-CoV-2 has provided an opportunity to use computational tools for drug discovery. Through virtual screening and simulation experiments, potential SARS-CoV-2 M-pro inhibitors have been identified. This study is of great importance in combating this pandemic.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Review
Biochemistry & Molecular Biology
Amit Kumar, Igor C. Fontana, Agneta Nordberg
Summary: Astrocytes play a crucial role in brain functioning and are involved in the pathophysiology of Alzheimer's disease and other neurodegenerative disorders through reactive astrogliosis.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Alen T. Mathew, Anurag T. K. Baidya, Bhanuranjan Das, Bharti Devi, Rajnish Kumar
Summary: This study used molecular dynamics simulation to investigate the effects of N-glycosylation on the folding and stability of tau protein, revealing the key residues involved in the folding process.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Clinical Neurology
Yang Yang, Wenjuan Zhang, Alexey G. Murzin, Manuel Schweighauser, Melissa Huang, Sofia Lovestam, Sew Y. Peak-Chew, Takashi Saito, Takaomi C. Saido, Jennifer Macdonald, Isabelle Lavenir, Bernardino Ghetti, Caroline Graff, Amit Kumar, Agneta Nordberg, Michel Goedert, Sjors H. W. Scheres
Summary: The high-resolution cryo-EM structures of A beta filaments with the Arctic mutation were reported in this study. Most of the filaments consist of two pairs of non-identical protofilaments, sharing a common substructure with the folds of type I and type II A beta 42. There are subtle conformational changes in the human Arctic folds, which may be due to the lack of a side chain at G22.
ACTA NEUROPATHOLOGICA
(2023)
Article
Biochemistry & Molecular Biology
Bharti Devi, Sumukh Satyanarayana Vasishta, Bhanuranjan Das, Anurag T. K. Baidya, Rahul Salmon Rampa, Manoj Kumar Mahapatra, Rajnish Kumar
Summary: Protein tyrosine phosphatases (PTPs) are enzymes that control cell activity and the dephosphorylation of tyrosine-phosphorylated proteins. Dysregulation of PTP1B has been linked to various diseases, and targeting PTP1B is considered a potential therapeutic approach. This study combines ligand-based and structure-based virtual screening to identify compounds that target PTP1B.
MOLECULAR DIVERSITY
(2023)
Article
Biochemistry & Molecular Biology
Mona-Lisa Malarte, Per-Goran Gillberg, Amit Kumar, Nenad Bogdanovic, Laetitia Lemoine, Agneta Nordberg
Summary: Recent studies have revealed the complexity and heterogeneity of tau pathology in Alzheimer's disease (AD) and primary tauopathies, challenging the classical classification approach. New second-generation tau PET tracers can help differentiate AD from non-AD tauopathies and show different binding properties.
MOLECULAR PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Anurag T. K. Baidya, Bhanuranjan Das, Bharti Devi, Bengt Langstroem, Hans agren, Taher Darreh-Shori, Rajnish Kumar
Summary: Various investigational studies have found that Proton Pump Inhibitors (PPIs) may increase the risk of developing Alzheimer's disease (AD) and non-AD related dementias. Using computational tools, this study provides mechanistic insights into the interaction between PPIs and the choline acetyltransferase (ChAT) binding pocket, which can help in designing novel ChAT ligands for the diagnosis and treatment of cholinergic dysfunction associated with AD.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Kailash Jangid, Bharti Devi, Ashrulochan Sahoo, Vijay Kumar, Ashish Ranjan Dwivedi, Suresh Thareja, Rajnish Kumar, Vinod Kumar
Summary: Alzheimer's disease (AD) is characterized by memory loss and cognitive impairment. Multi-target directed ligands (MTDLs) targeting cholinesterase and monoamine oxidase enzymes are being explored as an alternative treatment strategy. Computational approaches were used to identify potential MTDLs that inhibit acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B) enzymes. Three lead molecules with better binding scores than standard inhibitors were identified and further evaluation will be conducted in vitro and in vivo.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Physical
Bhanuranjan Das, Anurag T. K. Baidya, Bharti Devi, Tanmay Rom, Avijit Kumar Paul, Banita Thakur, Taher Darreh-Shori, Rajnish Kumar
Summary: This paper reports the synthesis and structural characterization of N-benzyl-4-(4-chlorophenyl)-2-oxobutanamide (1). The compound's 3D structure was determined through single crystal X-ray diffraction and optimized through DFT calculations. Interactions in the crystal structure and molecular properties were analyzed, and the compound's ability to modulate amyloid beta aggregation was investigated. The results provide insights for the design and synthesis of novel alpha-ketoamides as potential modulators of amyloid beta aggregation.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Biochemistry & Molecular Biology
Bhanuranjan Das, Alen T. T. Mathew, Anurag T. K. Baidya, Bharti Devi, Rahul Rampa Salmon, Rajnish Kumar
Summary: Alzheimer's disease (AD) is a severe and multifactorial disorder characterized by cognitive decline and neurodegeneration. The accumulation of tau protein is a major hallmark of AD and has been targeted as a potential drug target. This study used an AI-assisted virtual screening tool to identify potential tau aggregation inhibitors from a library of 12 million compounds. Molecular docking, pharmacokinetic prediction, and molecular dynamics simulations were performed to prioritize and evaluate the identified compounds, resulting in the discovery of several potential tau aggregation inhibitors.
MOLECULAR DIVERSITY
(2023)
Correction
Biochemistry & Molecular Biology
Mona-Lisa Malarte, Per-Goran Gillberg, Amit Kumar, Nenad Bogdanovic, Laetitia Lemoine, Agneta Nordberg
MOLECULAR PSYCHIATRY
(2023)
Review
Clinical Neurology
Igor C. Fontana, Amit Kumar, Agneta Nordberg
Summary: This review discusses the connection between the cholinergic and amyloid cascade hypotheses of Alzheimer's disease (AD) pathogenesis, focusing on the expression of alpha 7 nicotinic acetylcholine receptors (alpha 7nAChRs) by astrocytes and its correlation with amyloid-beta pathology. The search for biomarkers beyond amyloid-beta and tau in AD research has led to a recognition of the importance of astrocytes, which play a crucial role in metabolic homeostasis and respond rapidly to brain pathology in the early stages of AD. Upregulation of astrocytic alpha 7nAChRs is associated with A beta pathology in AD brains, making it a potential biomarker and target for therapeutic interventions.
NATURE REVIEWS NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Junhao Li, Amit Kumar, Bengt Langstrom, Agneta Nordberg, Hans Agren
Summary: In this study, the binding mechanisms of 10 PET tracers for PSP tau, CBD, and AD tau pathologies were investigated. The structure-activity relationships, binding preferences, intermolecular interactions, role of polar/charged residues, induced-fit mechanisms, grove closures, and folding patterns for these tracers in different tau fibrils were evaluated. The findings fill in the knowledge gap regarding the potential binding mechanisms of these tracers and are important for the design of highly selective novel PET tracers for tauopathies.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Mandeep Kaur, Akanksha Sharma, Harjeet Kaur, Manjari Singh, Bharti Devi, A. R. Naresh Raj, Vikas Sood, Ankur Pandey, Janeka Gartia, Rajnish Kumar, Adukamparai R. Suresh Babu, Gurpal Singh, Ravi Pratap Barnwal
Summary: This study identifies EH4 compound as a potential candidate against monkeypox infection based on its strong binding affinity with monkeypox viral proteins.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Lalita Dahiya, Rajiv Kumar, Anurag T. K. Baidya, Sunil Kumar, Rajnish Kumar, Sandip V. Pawar, Ashok Kumar Yadav
Summary: Diabetes mellitus is a global health urgency. In this study, novel N-substituted 2,4-thiazolidinedione derivatives were synthesized and tested for alpha-glucosidase inhibitory activities. Compounds A-12 and A-14 showed the highest potency and were further tested in vivo. The most potent compound also exhibited non-toxicity in cytotoxicity studies. Molecular docking, dynamic simulations, and ADME prediction studies were conducted to investigate the interactions and pharmacokinetic profiles. The development of these N-substituted TZD analogues provides new potential alpha-glucosidase inhibitors for diabetes treatment.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)