Article
Chemistry, Medicinal
Ruifang Jia, Jian Zhang, Chiara Bertagnin, Srinivasulu Cherukupalli, Wei Ai, Xiao Ding, Zhuo Li, Jiwei Zhang, Han Ju, Xiuli Ma, Arianna Loregian, Bing Huang, Peng Zhan, Xinyong Liu
Summary: The structural modifications at the 150-cavity of influenza virus neuraminidases can result in more potent oseltamivir derivatives, with compound 5c showing the most promising activity. In vitro and in vivo studies demonstrated low cytotoxicity and no acute toxicity of 5c, indicating its potential as a drug candidate.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Jiwei Zhang, Chuanfeng Liu, Ruifang Jia, Xujie Zhang, Jian Zhang, Chiara Bertagnin, Anna Bonomini, Laura Guizzo, Yuanmin Jiang, Huinan Jia, Shuzhen Jia, Xiuli Ma, Arianna Loregian, Bing Huang, Peng Zhan, Xinyong Liu
Summary: Introducing structurally diverse benzyl side chains at the C5-NH2 position of oseltamivir improves its binding affinity with neuraminidase and anti-influenza activity. We designed and synthesized novel oseltamivir derivatives with different N-heterocycle substituents that induce opening of the 150-loop of group-2 neuraminidases. Compound 6k showed broad-spectrum activity against wild-type neuraminidases and enhanced activity against H3N2 compared to oseltamivir carboxylate and zanamivir.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Pengfei Wang, Babayemi O. Oladejo, Chenning Li, Lifeng Fu, Shanshan Zhang, Jianxun Qi, Xun Lv, Xuebing Li
Summary: Various strategies have been explored for developing new and efficient NA inhibitors, including modifying antiviral drugs and targeting specific amino acid residues. A compound bearing a 3-phenylamino group demonstrated superior activity in inhibiting multiple NAs and showed potent antiviral replication in vitro.
Article
Chemistry, Medicinal
Hongqian Zhao, Siyuan Jiang, Zhifan Ye, Hongxi Zhu, Baichun Hu, Peipei Meng, Yanmei Hu, Huicong Zhang, Kuanglei Wang, Jun Wang, Yongshou Tian
Summary: The study designed a series of oseltamivir derivatives bearing hydrazide fragment, successfully targeting the 150 cavity, showing potent activity and satisfactory metabolic stability. This provides an important reference for potent inhibition against the H274Y mutant of NAs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ruifang Jia, Jiwei Zhang, Jian Zhang, Chiara Bertagnin, Anna Bonomini, Laura Guizzo, Zhen Gao, Xiangkai Ji, Zhuo Li, Chuanfeng Liu, Han Ju, Xiuli Ma, Arianna Loregian, Bing Huang, Peng Zhan, Xinyong Liu
Summary: Novel boron-containing derivatives were designed and synthesized to address drug resistance to influenza virus. Compound 2c exhibited strong antiviral activity against multiple influenza viruses, low cytotoxicity, and no acute toxicity.
Article
Chemistry, Medicinal
Ruifang Jia, Jiwei Zhang, Fangyuan Shi, Anna Bonomini, Camilla Lucca, Chiara Bertagnin, Jian Zhang, Chuanfeng Liu, Huinan Jia, Yuanmin Jiang, Xiuli Ma, Arianna Loregian, Bing Huang, Peng Zhan, Xinyong Liu
Summary: Two series of oseltamivir derivatives were designed, synthesized, and evaluated for their ability to inhibit neuraminidase. Compound 43b showed weaker or slightly improved inhibitory activity against wild-type neuraminidases compared to oseltamivir carboxylate. However, it displayed significantly more potent activity against mutant neuraminidases and exhibited equivalent or more potent antiviral activities in cellular assays. Additionally, 43b possessed improved physicochemical properties and ADMET properties compared to oseltamivir carboxylate. Therefore, it is considered a promising lead compound for further investigation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Chuanxiong Nie, Marlena Stadtmueller, Badri Parshad, Matthias Wallert, Vahid Ahmadi, Yannic Kerkhoff, Sumati Bhatia, Stephan Block, Chong Cheng, Thorsten Wolff, Rainer Haag
Summary: This study demonstrates the topology-matched design of heteromultivalent nanostructures as potent and broad-spectrum virus entry inhibitors based on the host cell membrane. By transferring heteromultivalent binding moieties to nanostructures with a bowl-like shape matching the viral surface, the inhibitors show superior performance in virus propagation inhibition. With identified binding sites on the S protein of SARS-CoV-2, this approach holds promise in developing effective inhibitors to prevent coronavirus infection.
Article
Chemistry, Medicinal
Jia-Jia Lang, You Lv, Bostjan Kobe, Hongfei Chen, Yan Tan, Limei Chen, Xuechuan Wang, Pengbing Mi, Xing Zheng, Ying-Wu Lin
Summary: We discovered a series of C-5 pyrazole-modified pyrrolopyrimidine derivatives as JAK1-selective inhibitors, where the potential hydrogen bond between the pyrazole group and E966 in JAK1 is the key point that enhances JAK1 selectivity. These compounds exhibit 10-to 20-fold JAK1 selectivity over JAK2 in enzyme assays. Compound 12b also exhibits excellent JAK1 selectivity in Ba/F3-TEL-JAK cellular assays, and may be a viable lead compound for the development of highly JAK1-selective inhibitors for immune and inflammatory diseases, as indicated by metabolism studies and the results of the hair growth model in mice.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Zhi Jian Zhong, Xiao Tong Hu, Li Ping Cheng, Xing Yong Zhang, Qiang Zhang, Ju Zhang
Summary: A new lead NA inhibitor, compound 4b, was discovered in this study, showing potent inhibitory activity against NA and avian influenza H5N1. The results may offer insightful help for the development of new NA inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Konstantin Andreev, Jeremy C. Jones, Patrick Seiler, Ahmed Kandeil, Jasmine C. M. Turner, Subrata Barman, Adam M. Rubrum, Richard J. Webby, Elena A. Govorkova
Summary: The antiviral susceptibility of currently circulating highly pathogenic avian influenza A(H5N1) viruses was assessed using genotypic and phenotypic approaches. The majority of the viruses retain susceptibility to antiviral drugs, but novel mutations have been identified that reduce the inhibitory effects of certain drugs.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Medicine, General & Internal
Sofia Tejada, Miia Jansson, Candela Sole-Lleonart, Jordi Rello
Summary: Neuraminidase inhibitors (NAIs) therapy significantly reduced the time to clinical resolution, total influenza-related complications, acute otitis media and need for antibiotic treatment. While reductions in mortality, pneumonia, asthma exacerbations, and hospitalization rates only demonstrated a trend benefit with NAIs treatment. The most significant adverse event associated with NAIs was an increase in nausea and vomiting.
EUROPEAN JOURNAL OF INTERNAL MEDICINE
(2021)
Article
Immunology
Takuji Komeda, Takahiro Takazono, Naoki Hosogaya, Eriko Ogura, Masakazu Fujiwara, Hideyuki Miyauchi, Yoshikazu Ajisawa, Shinpei Iwata, Hideaki Watanabe, Keiichi Honda, Yoshitake Kitanishi, Kanae Hara, Hiroshi Mukae
Summary: The study found that baloxavir may help reduce household transmission of influenza compared to oseltamivir. However, no similar reduction was shown in comparison to inhalant medications, which may be due to unmeasured confounding factors related to differences in administration route.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Microbiology
Leo Y. Y. Lee, Jie Zhou, Paulina Koszalka, Rebecca Frise, Rubaiyea Farrukee, Keiko Baba, Shahjahan Miah, Takao Shishido, Monica Galiano, Takashi Hashimoto, Shinya Omoto, Takeki Uehara, Edin J. Mifsud, Neil Collinson, Klaus Kuhlbusch, Barry Clinch, Steffen Wildum, Wendy S. Barclay, Aeron C. Hurt
Summary: This study evaluated the fitness of influenza viruses with reduced baloxavir susceptibility in ferrets. The results showed that these viruses had slightly reduced within-host fitness compared to wild-type viruses, but significant differences in between-host fitness, suggesting a compromised transmission ability.
Review
Chemistry, Medicinal
Kuanglei Wang, Huicong Zhang, Yongshou Tian
Summary: This review covers influenza drugs, mutation types of neuraminidase, molecular mechanisms of drug resistance, strategies to enhance drug susceptibility, and alternative therapies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Yu-Jen Chang, Cheng-Yun Yeh, Ju-Chien Cheng, Yu-Qi Huang, Kai-Cheng Hsu, Yu-Feng Lin, Chih-Hao Lu
Summary: Eradicating influenza A virus (IAV) is challenging due to its genetic variability. Hemagglutinin (HA) is a promising target for anti-influenza drugs, but its complex structure has hindered structural characterization. Computational analysis identified potential HA inhibitors in the National Cancer Institute database.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Jiangying Cao, Jie Zang, Xiujie Kong, Chunlong Zhao, Ting Chen, Yingying Ran, Hang Dong, Wenfang Xu, Yingjie Zhang
BIOORGANIC & MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Xuewu Liang, Jie Zang, Xiaoyang Li, Shuai Tang, Min Huang, Meiyu Geng, C. James Chou, Chunpu Li, Yichun Cao, Wenfang Xu, Hong Liu, Yingjie Zhang
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Hang Dong, Hao Yin, Chunlong Zhao, Jiangying Cao, Wenfang Xu, Yingjie Zhang
Review
Chemistry, Medicinal
Chunlong Zhao, Hang Dong, Qifu Xu, Yingjie Zhang
EXPERT OPINION ON THERAPEUTIC PATENTS
(2020)
Article
Chemistry, Medicinal
Yugang Yan, Qifu Xu, Chunlong Zhao, Hang Dong, Wenfang Xu, Yingjie Zhang
DRUG DEVELOPMENT RESEARCH
(2020)
Article
Cell Biology
Qifu Xu, Chunxi Liu, Jie Zang, Shuai Gao, C. James Chou, Yingjie Zhang
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Shunda Li, Chunlong Zhao, Guozhen Zhang, Qifu Xu, Qian Liu, Wei Zhao, C. James Chou, Yingjie Zhang
Summary: The novel pyrrolo[2,3-d]pyrimidine-based HDAC inhibitors demonstrated potent inhibitory activities and selectivities against HDAC6, showing superior antiproliferative activity against human multiple myeloma cell lines while maintaining low cytotoxicity. In addition, one representative compound showed good metabolic stability and in vivo anti-multiple myeloma potency in a xenograft model.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Anil Kumar Marapaka, Priyanka Sankoju, Guozhen Zhang, Yongzheng Ding, Chunhua Ma, Vijaykumar Pillalamarri, Renu Sudhakar, Bharati Reddi, Puran Singh Sijwali, Yingjie Zhang, Anthony Addlagatta
Summary: This study describes the development of peptide-mimetic hydroxamates as antimalarial drugs, and compound 26 shows potent antimalarial activity and selectivity. The crystal structures provide insights into the molecular basis of its inhibitory activity and offer important clues for the design of selective and dual antimalarial agents.
CHINESE CHEMICAL LETTERS
(2022)
Review
Chemistry, Medicinal
Qifu Xu, Guozhen Zhang, Qian Liu, Shunda Li, Yingjie Zhang
Summary: This review discusses the recent patents on KRAS(G12C) inhibitors, focusing on their chemical structures, mechanisms of action, pharmacokinetic properties, and potential clinical applications. Significant breakthroughs have been made in the development of KRAS inhibitors in the past few years, with several compounds entering clinical trials and receiving FDA approval. However, acquired resistance is expected to be an inevitable challenge. Emerging KRAS(G12C) inhibitors, with their strengths and limitations, will undoubtedly enhance our understanding of KRAS biology and targeted therapy, providing insights into the development of inhibitors for other KRAS mutations.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2022)
Article
Chemistry, Medicinal
Qian Liu, Hang Dong, Wei Zhao, Guozhen Zhang, Shunda Li, Qifu Xu, Yingjie Zhang
Summary: A novel series of APN and AKT dual inhibitors were developed from the clinical AKT inhibitor AZD5363, with most compounds showing remarkable APN inhibitory activities. These compounds also exhibited moderate AKT inhibitory potencies, indicating potential therapeutic value in cancer treatment with balanced APN and AKT dual inhibition. The superior APN inhibitory activities of selected compounds were confirmed at the cellular level, with one compound effectively inhibiting the phosphorylation of GSK3 beta, an intracellular substrate of AKT.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Editorial Material
Pharmacology & Pharmacy
Zhi Shi, Ning Wang, Ying-Jie Zhang, Yi-Chao Zheng
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Fengling Liu, Chunxi Liu, Qipeng Chai, Chunlong Zhao, Hongwei Meng, Xia Xue, Tso-pang Yao, Yingjie Zhang
Summary: In our previous research, a compound named 1 showed significant anti-tumor activity due to its HDAC inhibitory and NO-donating properties. Further study revealed that compound 1 could increase acetyl histones and acetyl & alpha;-tubulin levels by irreversibly inhibiting class I HDACs and HDAC6. Modification of compound 1 led to the development of compound 4, which selectively and irreversibly inhibited intracellular HDAC6 and exhibited improved therapeutic index compared to ACY-241.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Jiangying Cao, Chunlong Zhao, Hang Dong, Qifu Xu, Yingjie Zhang
Summary: A new series of pyrazoline-based derivatives were synthesized, among which compound 2k showed promising APN inhibitory activity and effectively prevented pulmonary metastasis of H22 hepatoma cells in vivo, indicating its potential as an anti-tumor agent.
Article
Biochemistry & Molecular Biology
Qin'ge Ding, Chunxi Liu, Chunlong Zhao, Hang Dong, Qifu Xu, C. James Chou, Yingjie Zhang
BIOORGANIC CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Jiangying Cao, Wei Zhao, Chunlong Zhao, Qian Liu, Shunda Li, Guozhen Zhang, C. James Chou, Yingjie Zhang