Article
Biochemistry & Molecular Biology
Sergio Jurado, Beatriz Dominguez-Perez, Ona Illa, Jan Balzarini, Felix Busque, Ramon Alibes
Summary: The enantioselective preparation of the two isomers of 4-hydroxy-2-cyclohexanone derivatives was achieved through asymmetric transfer hydrogenation reactions. A stereoselective route to a cytosine analogue was described, showing selectivity for herpes simplex virus TKs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Andrea C. Ojeda-Porras, Vincent Roy, Luigi A. Agrofoglio
Summary: Nucleoside analogues have been widely used in antiviral therapy, and various families of nucleoside analogues have been developed through structural modifications to improve their efficacy and selectivity. Carbocyclic nucleoside analogues, which have shown potent antiviral activity against HIV and HBV, have attracted increasing interest. This review article discusses recent advances in the chemistry of selected five-membered ring carbocyclic nucleosides.
Article
Chemistry, Organic
K. A. Krishnakumar, Ravi S. Lankalapalli
Summary: A convergent synthetic route for BCX-1777 and BCX-4430 was developed using a Boc-protected 2-pyrrolidinone and a dihalogenated pyrrolopyrimidine as key starting materials. The synthesis involved chemoselective cross-coupling, Luche reduction, and mesylation to achieve the stereoselective formation of an advanced intermediate, which served as a precursor for synthesizing BCX-1777 and BCX-4430 with good overall yields.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Young Eum Hyun, Hong-Rae Kim, Lak Shin Jeong
Summary: Asymmetric synthesis was used to synthesize conformationally locked south (S) and north (N) analogues of sugars, with different synthetic strategies employed to obtain the two conformations.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Maria De Fenza, Anna Esposito, Giovanni Talarico, Graciela Andrei, Robert Snoeck, Daniele D'Alonzo, Annalisa Guaragna
Summary: In this study, six-membered nucleoside analogues with a piperidine ring as the preorganized (deoxy)ribose bioisostere were synthesized and evaluated for their antiviral activity. The 5-iododeoxyuridine analogue showed activity against all tested DNA viruses. DFT analysis and pH-dependent NMR experiments suggested that the antiviral activity was attributed to the biomimetic character of the piperidine ring, which can mimic the conformation of natural nucleosides when interacting with viral enzymes.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Organic
An-Di Liu, Zhao-Li Wang, Li Liu, Liang Cheng
Summary: The direct C5 (hetero)arylation of uracil and uridine substrates with (hetero)aryl diazonium salts under photoredox catalysis with blue light was reported. The coupling proceeds efficiently with good functional group tolerance at room temperature in aqueous solution without transition-metal components. A plausible radical mechanism has been proposed for this reaction.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Marta Denel-Bobrowska, Agnieszka B. B. Olejniczak
Summary: This review provides an overview of synthetic antiviral agents not associated with nucleosides that have been developed and introduced to preclinical and clinical trials for human viruses over the last decade. The compounds are classified based on their antiviral mechanism of action and the article briefly summarizes their biological targets and clinical applications. Understanding the activity of drugs against specific molecular targets is key to researching new antiviral compounds and repurposing approved drugs for clinical use. The paper also discusses the future directions of antiviral therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Samir Mohamed Awad, Shima Mahmoud Ali, Yara Essam Mansour, Samar Said Fatahala
Summary: Newly synthesized nucleoside drugs show promising activity against HSV-1, offering a potential solution to the problems associated with current medications.
Article
Biochemistry & Molecular Biology
Maria Elena Marcocci, Bianka Gabriela Jackowska, Carla Prezioso, Virginia Protto, Marta De Angelis, Francesco Saverio Di Leva, Bruno Casciaro, Alfonso Carotenuto, Maria Luisa Mangoni, Anna Teresa Palamara, Valeria Pietropaolo, Giovanna De Chiara, Lucia Nencioni
Summary: Natural occurring peptides like temporin G (TG) could be potential drugs to combat diseases caused by HSV-1 and JCPyV.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Er-Jun Hao, Gong-Xin Li, Yu-Ru Liang, Ming-Sheng Xie, Dong-Chao Wang, Xiao-Han Jiang, Jia-Yi Cheng, Zhi-Xian Shi, Yang Wang, Hai-Ming Guo
Summary: The study designed, synthesized, and evaluated 103 novel acyclic nucleosides for their anticancer activities, with compound 9b showing promising inhibitory effects on colon cancer cells. All (R)-configured derivatives displayed stronger anticancer activity, with compound 9b inducing apoptosis and inhibiting colony formation. Importantly, compound 9b exhibited low systemic toxicity and inhibited tumor growth in a mouse model, suggesting it as a potential lead compound for future anticancer drug discovery.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Microbiology
Yuko Sato, Tadahiro Suenaga, Makoto Kobayashi, Nozomu Miyazaki, Takato Suzuki, Ken Ishioka, Tatsuo Suzutani
Summary: This study identified AMNV-resistant HSV-1 and HSV-2 viruses with amino acid substitutions in UL5 and UL52, downstream of motif IV. The most frequent mutations were UL5 K356N in HSV-1 and K355N in HSV-2. Recombinant viruses with single amino acid substitutions showed various levels of AMNV resistance, with UL5 K356N mutant maintaining equivalent viral growth and virulence as the parent virus.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Biotechnology & Applied Microbiology
Hyla Allouche-Arnon, Olga Khersonsky, Nishanth D. Tirukoti, Yoav Peleg, Orly Dym, Shira Albeck, Alexander Brandis, Tevie Mehlman, Liat Avram, Talia Harris, Nirbhay N. Yadav, Sarel J. Fleishman, Amnon Bar-Shir
Summary: This research utilizes the MRI system GeneREFORM for two-color imaging, improving the detection of transgene expression in live animals. By designing orthogonal reporter genes and reporter probes, dynamic proton exchange MRI imaging is achieved, paving the way for future deep-tissue multiplexed imaging of gene expression in live animals.
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jianyang Han, Christina Funk, Juri Eyberg, Susanne Bailer, Clemens Richert
Summary: Challenges posed by novel viruses or new strains call for new antiviral agents. This study introduces a new class of strongly pairing pyrimidine analogs, showing antiviral activity against Herpes simplex virus type 1, with potential for becoming active pharmaceutical ingredients.
CHEMISTRY & BIODIVERSITY
(2021)
Article
Chemistry, Medicinal
Yuqing Xu, Elisabetta Groaz, Jerome Rihon, Piet Herdewijn, Eveline Lescrinier
Summary: Molecular dynamics simulations revealed the favorable interactions between xylose nucleosides with a phosphonate moiety and specific residues at the active site of the RNA-dependent RNA-polymerase of Enterovirus 71. Xylosyl nucleoside phosphonates containing different nucleobases were synthesized and tested for antiviral activity, with the adenine-containing analogue showing good activity against measles virus and enterovirus-68 without cytotoxicity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Roberta Bivacqua, Marilia Barreca, Virginia Spano, Maria Valeria Raimondi, Isabella Romeo, Stefano Alcaro, Graciela Andrei, Paola Barraja, Alessandra Montalbano
Summary: Viruses are responsible for causing various pathological conditions, with efforts made to identify selective viral targets for developing efficient therapeutics. Polymerases are attractive targets due to their crucial role in the viral life cycle. This overview focuses on non-nucleoside triazole-based compounds discovered in the past fifteen years as potential viral polymerase inhibitors, highlighting the structure-activity relationships necessary for developing effective antiviral agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Shuai Xu, Yuanyu Wang, Maoyun Yu, Dandan Wang, Yingquan Liang, Yuanli Chen, Chenzhong Liao, Zhouling Xie, Buchang Zhao, Jihong Han, Yajun Duan, Xiaoxiao Yang
BIOMEDICINE & PHARMACOTHERAPY
(2020)
Article
Medicine, Research & Experimental
Xuerui Wang, Zequn Yin, Peichang Cao, Shihong Zheng, Yuanli Chen, Maoyun Yu, Chenzhong Liao, Zhongyuan Zhang, Yajun Duan, Jihong Han, Shuang Zhang, Xiaoxiao Yang
Summary: Alzheimer's disease (AD) is the most common neurodegenerative disease in aging population. The traditional Chinese medicine NaoXinTong Capsule (NXT) has been shown to improve spatial memory impairment and cognitive decline in AD mice by reducing p-Tau levels and A beta accumulation in the brain. This neuroprotective effect is achieved by inhibiting inflammatory cytokines and mediators, thereby suggesting the potential application of NXT for AD treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Chemistry, Medicinal
Zhouling Xie, Xiaoxiao Yang, Yajun Duan, Jihong Han, Chenzhong Liao
Summary: Kinase inhibitors have been successful in treating various diseases beyond cancer, including autoimmune diseases and inflammatory diseases. Several non-oncologic small-molecule kinase inhibitors have been approved, with more in development for different applications.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Wanheng Zhang, Kuojun Zhang, Yiwu Yao, Yunyao Liu, Yong Ni, Chenzhong Liao, Zhengchao Tu, Yatao Qiu, Dexiang Wang, Dong Chen, Lei Qiang, Zheng Li, Sheng Jiang
Summary: The study developed the first compounds that simultaneously inhibit NAMPT and EGFR, with compound 28 showing good inhibitory effects and demonstrating anti-tumor efficacy in vitro and in vivo. This research provides promising leads for the development of novel anti-tumor agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yi Chen, Wenquan Hu, Qi Li, Shiwei Zhao, Dan Zhao, Shuang Zhang, Zhuo Wei, Xiaoxiao Yang, Yuanli Chen, Xiaoju Li, Chenzhong Liao, Jihong Han, Qing Robert Miao, Yajun Duan
Summary: Reduced expression of NGBR in the liver is associated with obesity-related T2D in patients and mice, while overexpression of NGBR can improve insulin sensitivity and reduce beta-cell loss.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Haiyan Kong, Xianshe Meng, Rui Hou, Xiaoxiao Yang, Jihong Han, Zhouling Xie, Yajun Duan, Chenzhong Liao
Summary: This study developed 1-(prop-2-yn-1-ylamino)-2,3-dihydro-1H-indene-4-thiol derivatives as hMAO-B inhibitors, among which K8 and K24 showed promising inhibitory activities and selectivity. These compounds have potential applications for Parkinson's disease treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Rui Hou, Yan He, Guangwei Yan, Shuzeng Hou, Zhouling Xie, Chenzhong Liao
Summary: In humans, over three hundred enzymes dependent on zinc have been identified, some of which are considered valuable targets for drug discovery. Many drugs targeting these zinc enzymes have been marketed for treating various diseases. This review discusses drug discovery and development based on zinc enzymes, including biological functions, pathogenic roles, inhibitors, binding modes, and challenges in developing zinc enzyme inhibitors for human disorders.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Agriculture, Multidisciplinary
Yun-Yang Zhu, Kiran Thakur, Jing-Yu Feng, Jian-Guo Zhang, Fei Hu, Carlos L. Cespedes-Acuna, Chenzhong Liao, Zhao-Jun Wei
Summary: The study reveals that B2FS can effectively alleviate the detrimental effects of ariboflavinosis, including oxidative stress-mediated liver injury, chronic intestinal inflammation, and gut dysbiosis, through the activation of the Nrf2 signaling pathway in the B-2 depletion-repletion mice model.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Zhouling Xie, Shuzeng Hou, Xiaoxiao Yang, Yajun Duan, Jihong Han, Qin Wang, Chenzhong Liao
Summary: Inhibition of CDK has proven to be an effective strategy for treating various diseases, particularly cancer. However, the development of CDK inhibitors has faced difficulties and misunderstandings, such as inadequate understanding of CDK's biological functions and the overlooking of the importance of multi-CDK inhibitors. This article summarizes and discusses these issues, aiming to facilitate the discovery of more useful CDK inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Ningning Yao, Zhiping Jia, Yongbin Tian, Shuzeng Hou, Xiaoxiao Yang, Jihong Han, Yajun Duan, Chenzhong Liao, Yi Kong, Zhouling Xie
Summary: In this study, novel selective FXIa inhibitors were identified through structure-based drug design strategies, which have extra interactions with the S2 subsite of FXIa. Compound 35 displayed good inhibitory activity against FXIa and high selectivity over PKal and other serine proteases. In vivo experiments showed that 35 exhibited significant antithrombotic activity without increasing bleeding risk and toxicity in mice, suggesting it as a promising candidate for further research.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Yang Shu, Yajing Liu, Shirong Bian, Zhouling Xie, Chenzhong Liao
Summary: Polo-like kinase 4 (PLK4) is a key regulator of the cell cycle that controls centrosome duplication and mitosis. It has been identified as a promising target for cancer therapy, and PLK4 inhibitors have shown potential for treating various cancers and other PLK4-associated human disorders. In addition, PLK4 may have a role in sensitizing DNA damage, thus improving the efficacy of chemotherapy. However, there is still limited understanding of PLK4, and further research is needed to identify novel mechanisms.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Dai-gang Yang, Yong-yao Gao, Ze-qun Yin, Xue-rui Wang, Xian-she Meng, Ting-feng Zou, Ya-jun Duan, Yuan-li Chen, Chen-zhong Liao, Zhou-ling Xie, Xiao-dong Fan, Lu Sun, Ji-hong Han, Xiao-xiao Yang
Summary: Sensitization of central pain and inflammatory pathways plays a critical role in migraine, and this study demonstrates that the HIF-1 alpha/NF-kappa B/inflammation pathway is involved in this process. Roxadustat, a HIF-1 alpha stabilizer, shows potential as a therapeutic option for migraine by ameliorating migraine-like behaviors and inhibiting central pain sensitization.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Chemistry, Multidisciplinary
Ting-feng Zou, Zhi-gang Liu, Pei-chang Cao, Shi-hong Zheng, Wen-tong Guo, Tian-xiang Wang, Yuan-li Chen, Ya-jun Duan, Qing-shan Li, Chen-zhong Liao, Zhou-ling Xie, Ji-hong Han, Xiao-xiao Yang
Summary: The study investigated the therapeutic effects of fisetin, a natural flavonoid, on kidney injury caused by diabetic atherosclerosis. The results showed that fisetin effectively attenuated diabetes-exacerbated atherosclerosis and ameliorated atherosclerosis-enhanced diabetic kidney injury. Fisetin reduced oxidative stress, glycosylation end products, and inflammation while regulating the expression of proteins involved in extracellular matrix and renal fibrosis.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Chemistry, Medicinal
Zhouling Xie, Zhiwei Meng, Xiaoxiao Yang, Yajun Duan, Qin Wang, Chenzhong Liao
Summary: This article introduces FXIa as an effective and safe target for anticoagulant discovery, and discusses the recent progress in the design, discovery, structure-activity relationships, and development of small-molecule FXIa inhibitors. The strategies for identifying more selective and druggable inhibitors are also provided, which may lead to the development of more useful anticoagulant therapies.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Shihong Zheng, Peichang Cao, Zequn Yin, Xuerui Wang, Yuanli Chen, Maoyun Yu, Baocai Xu, Chenzhong Liao, Yajun Duan, Shuang Zhang, Jihong Han, Xiaoxiao Yang
Summary: Apigenin can improve cholestasis induced by DDC by reducing inflammation and oxidative damage, and improving bile acid metabolism, indicating its potential application for cholestasis treatment.