Article
Chemistry, Medicinal
Jin-Ling Huo, Shuai Wang, Xiao-Han Yuan, Bin Yu, Wen Zhao, Hong-Min Liu
Summary: Compound 6i showed potent anti-proliferative activity against MGC-803 with good safety in vivo. Mechanistic studies revealed that 6i induced apoptosis in MGC-803 cells through multiple pathways, suggesting its potential as a template for anti-cancer agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Stephanie Federico, Margherita Persico, Letizia Trevisan, Chiara Biasinutto, Giovanni Bolcato, Veronica Salmaso, Tatiana Da Ros, Teresa Gianferrara, Filippo Prencipe, Sonja Kachler, Karl-Norbert Klotz, Sabrina Pacor, Stefano Moro, Giampiero Spalluto
Summary: This study identified a new selective antagonist for the A(3) adenosine receptor, which showed pro-proliferative effects on cancer cells. These findings provide a foundation for further investigation of its mechanism and potential therapeutic applications.
Article
Chemistry, Medicinal
Maria Chiara Pismataro, Tommaso Felicetti, Chiara Bertagnin, Maria Giulia Nizi, Anna Bonomini, Maria Letizia Barreca, Violetta Cecchetti, Dirk Jochmans, Steven De Jonghe, Johan Neyts, Arianna Loregian, Oriana Tabarrini, Serena Massari
Summary: The study identified 1,2,4-triazolo[1,5-a] pyrimidine (TZP) as a suitable scaffold for developing anti-influenza virus compounds, with compound 22 showing high activity. Furthermore, the research highlighted the potential of TPZ scaffold in the search for anti-coronavirus agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Killian Oukoloff, Goodwell Nzou, Carmine Varricchio, Bobby Lucero, Thibault Alle, Jane Kovalevich, Ludovica Monti, Anne-Sophie Cornec, Yuemang Yao, Michael J. James, John Q. Trojanowski, Virginia M-Y Lee, Amos B. Smith, Andrea Brancale, Kurt R. Brunden, Carlo Ballatore
Summary: Triazolopyrimidines compounds show potential in treating Alzheimer's disease and neurodegenerative tauopathies, with the fragment at C6 playing a critical role in determining MT stability and integrity in cells. A new set of structurally modified analogues has been designed, synthesized, and evaluated, showing improved properties, activity, and pharmacokinetics compared to existing lead compounds.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Mounir A. A. Mohamed, Adnan A. Bekhit, Omyma A. Abd Allah, Asmaa M. Kadry, Tamer M. Ibrahim, Salma A. Bekhit, Kikuko Amagase, Ahmed M. M. El-Saghier
Summary: A series of novel [1,2,4]-triazole derivatives bearing amino acids were synthesized using lemon juice as an acidic catalyst under green chemistry conditions. These compounds showed promising antibacterial activity against standard bacteria and multidrug resistant strains, with better MIC values compared to reference drugs. Some compounds exhibited bacteriostatic activity and high selectivity towards antimicrobial activity against specific bacteria, indicating a good safety profile.
Article
Chemistry, Medicinal
Lin Chen, Tang-Yang Ji, Xian-Sen Huo, Zhi-Yu Zeng, Wei-Xuan Ye, Chen-Chen Dai, Yu-Qi Zhang, Wen-Wei You, Pei-Liang Zhao
Summary: A series of new compounds were designed and synthesized as potential tubulin polymerization inhibitors, among which one compound showed excellent antiproliferative activity and selectivity against cancer cells, as well as significant tubulin polymerization inhibitory activity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Xian-Sen Huo, Xie-Er Jian, Jie Ou-Yang, Lin Chen, Fang Yang, Dong-Xin Lv, Wen-Wei You, Jin-Jun Rao, Pei-Liang Zhao
Summary: The novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine derivatives showed great potential as tubulin polymerization inhibitors, with high antiproliferative activity and selectivity against cancer cells. These compounds inhibit tumor cell growth by affecting the cell cycle, inducing apoptosis, and inhibiting tubulin polymerization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Guang-Xi Yu, Ying Hu, Wei-Xin Zhang, Xin-Yi Tian, Sai-Yang Zhang, Yan Zhang, Shuo Yuan, Jian Song
Summary: In this study, a series of [1,2,4]triazolo[1,5-a]pyrimidine indole derivatives were designed and synthesized as anticancer agents. Compound H12 showed the most potent antiproliferative activities against MGC-803, HCT-116, and MCF-7 cells, and it inhibited the ERK signaling pathway, induced cell apoptosis, and regulated cell cycle-related proteins.
Article
Engineering, Environmental
Hui Dou, Peng Chen, Lu Hu, Chunlin He, Siping Pang
Summary: Three neutral energetic compounds with a novel oxygen-containing fused ring were synthesized and fully characterized in this study. Their detonation performances were evaluated based on their decomposition temperature, density, and impact sensitivity.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Papisetti Venkatesham, Mansi Kalonia, Akanksha Ashok Sangolkar, Anwita Mudiraj, Phanithi Prakash Babu, Rajeswar Rao Vedula
Summary: A novel one-pot synthesis method for potential anticancer triazolopyrimidines was reported. The synthesized compounds showed concentration dependent inhibition against breast cancer cells, and one compound exhibited good binding interaction with amino acid residues in molecular docking simulation.
Article
Biochemistry & Molecular Biology
Omid Kohandel, Seddigheh Sheikhi-Mohammareh, Fatemeh Oroojalian, Toktam Memariani, Joel Mague, Ali Shiri
Summary: New selenopheno[2,3-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives were synthesized via Dimroth rearrangement and their anticancer activity was tested, with the S-hexyl-substituted compound showing the strongest cytotoxic potency among the compounds tested.
MOLECULAR DIVERSITY
(2022)
Article
Chemistry, Medicinal
Thibault Alle, Carmine Varricchio, Yuemang Yao, Bobby Lucero, Goodwell Nzou, Stefania Demuro, Megan Muench, Khoa D. Vuong, Killian Oukoloff, Anne-Sophie Cornec, Karol R. Francisco, Conor R. Caffrey, Virginia M. -Y. Lee, Amos B. Smith III, Andrea Brancale, Kurt R. Brunden, Carlo Ballatore
Summary: Researchers designed, synthesized, and evaluated a series of new triazolo[1,5-a]-pyrimidine compounds, and further elucidated the structure-activity relationships of these compounds through matched molecular pair analyses and computational studies. The study identified novel microtubule-stabilizing triazolo[1,5-a]-pyrimidine candidates that exhibited favorable ADME-PK properties, including brain penetration and oral bioavailability, as well as brain pharmacodynamic activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Zihao Li, Kongxi Qiu, Xiao Yang, Wei Zhou, Qian Cai
Summary: A base-promoted tandem SNAr/Boulton-Katritzky rearrangement is developed for the formation of functionalized [1,2,4]triazolo[1,5-a]pyridines from 1,2,4-oxadiazol-3-amines or 3-aminoisoxazoles with 2-fluoropyridines.
Article
Chemistry, Organic
Jia Hui Ng, Anton Dolzhenko
Summary: A microwave-assisted method was developed for the synthesis of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines from 5-aminopyrazolyl-4-carbonitriles, orthoesters, and hydrazides in one pot. The method uses anisole as a green media and allows for diverse pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine preparation with variations in the structure of each substrate. The catalyst-free one-pot protocol, short reaction time, and convenient work-up are additional advantageous features of this method.
Article
Chemistry, Applied
Denis A. Gazizov, Alexander S. Steparuk, Nadezhda S. Demina, Ekaterina F. Zhilina, Oleg S. Eltsov, German S. Lebedkin, Gennady L. Rusinov, Alexey E. Alexandrov, Alexey R. Tameev
Summary: Novel [1,2,4]triazolo[1,5-a]pteridine derivatives were synthesized for the creation of test systems based on them. It was found that the substituent in the pyrazine ring of the TPt framework had a stronger influence on photophysical properties than that in the triazole ring. Although the fluorescence quantum yields of the compounds were generally low (3-23%), some of the TPt derivatives showed sensitivity to trace amounts of organic peroxides, making them promising for test systems. Additionally, the low-lying HOMO energy levels, energy gap values, and electron mobility of TPt materials suggest their potential use in organic electronic devices.
Review
Pharmacology & Pharmacy
Yihui Song, Xiaoke Yang, Bin Yu
Summary: Drug repurposing is an attractive strategy for finding new indications for existing drugs. Three approved antidepressants have shown potential in clinical trials for cancer treatment. By conducting further medicinal chemistry research, several TCP-based inhibitors of the histone lysine specific demethylase 1 enzyme have been discovered, showing promise for cancer treatment. Repurposing antidepressants could be a promising strategy for cancer treatment.
DRUG DISCOVERY TODAY
(2022)
Review
Chemistry, Medicinal
Yihui Song, Huiqing Zhang, Xiaoke Yang, Yuting Shi, Bin Yu
Summary: Lysine-specific demethylase 1 (LSD1/KDM1A) has emerged as a promising epigenetic target for disease treatment. This review provides an update on LSD1 inhibitors, including natural products, synthetic compounds, and cyclic peptides reported in 2021. The design strategies, structure-activity relationships, binding model analysis, and modes of action are discussed. Highlights include the repurposing of FDA-approved drugs as reversible LSD1 inhibitors, the identification of clinical candidates for neuro-developmental disorders, and the enhanced anti-cancer effects of dual inhibitors targeting both LSD1 and HDAC6 or tubulin.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Kai Tang, Min Zhao, Ya-Hong Wu, Qiong Wu, Shu Wang, Yu Dong, Bin Yu, Yihui Song, Hong-Min Liu
Summary: The study presents a highly potent, selective, and cellularly active allosteric SHP2 inhibitor TK-453, which modulates the phosphorylation of cell signaling pathways by inhibiting the phosphatase activity of SHP2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Kai Tang, Bo Wang, Bin Yu, Hong-Min Liu
Summary: Indoleamine 2,3-dioxygenase 1 (IDO1) is an important immunosuppressive enzyme in cancer therapy. Multiple IDO1 inhibitors have entered clinical trials, and PROTAC-based degraders also show promise for cancer treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yingying Zhang, Liuqing Cui, Wangji Chen, Benny Danilo Belviso, Bin Yu, Yunpeng Shen
Summary: This study developed an integrated approach to screen FBXW8 inhibitors and identified three compounds with potential as therapeutic candidates for CRL7-related cancers.
MOLECULAR DIVERSITY
(2023)
Article
Chemistry, Medicinal
Ruo-Lan Zhou, Zhiran Ju, Christophe Pannecouque, Erik De Clercq, Shuai Wang, Fen-Er Chen
Summary: In this study, novel cyclopropyl-substituted HEPT analogs were developed to improve their potency and safety as non-nucleoside inhibitors of HIV-1 reverse transcriptase. Compound 9h exhibited significantly increased inhibitory activity against wild-type HIV-1 (EC50=0.017μM) compared to the lead compound 2. It also showed reduced cytotoxicity with a higher selectivity index (SI>2328) and promising pharmacokinetics profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Yihui Song, Shu Wang, Bin Yu
Summary: Small molecules targeting the FAD-dependent LSD family have shown promise as therapeutic candidates for various diseases. Nine clinical candidates are currently being investigated for their ability to treat cancers and neurodegenerative diseases. In addition, noncatalytic functions of LSDs are being explored as a new strategy for disease treatment. This Perspective provides a comprehensive analysis of the LSD family, including its structure, function, and different types of inhibitors, with the aim of identifying new druggable targets for LSD inhibitors. The strategies for targeting LSD's demethylase-independent functions are also briefly discussed.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Guanjun Dong, Jiahui Zuo, Junlin Yu, Jiale Xu, Ge Gao, Guo-Bo Li, Wen Zhao, Bin Yu
Summary: This study presents a new triazolopyrimidine-based EED inhibitor that disrupts embryonic ectoderm development and inhibits tumor growth with excellent pharmacokinetic profiles. It has the potential for lymphoma treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Xiaopeng Peng, Ziwen Yu, Goverdhan Surineni, Bulian Deng, Meizhu Zhang, Chuan Li, Zhiqiang Sun, Wanyi Pan, Yao Liu, Shenglan Liu, Bin Yu, Jianjun Chen
Summary: In this study, a series of novel HDAC6 inhibitors containing polycyclic aromatic rings were discovered and evaluated for their pharmacological activities. Compound 10c showed high inhibitory activity against HDAC6 and selectivity over HDAC3. It also exhibited decent antiproliferative activity against cancer cell lines and demonstrated potential as an anti-cancer agent. Furthermore, the combination of 10c with a PD-L1 inhibitor showed promising results in reducing tumor burden and enhancing the anti-tumor immune response.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Ya-Li Sang, Christophe Pannecouque, Erik De Clercq, Shuai Wang, Fen-Er Chen
Summary: A series of novel biphenyl-DAPY derivatives were developed using the fragment-hopping strategy to enhance the anti-resistance efficacy of a non-nucleoside reverse transcriptase inhibitor (NNRTI). Most of the compounds exhibited improved anti-HIV-1 potency, with compound 8r showing exceptional potency against wild-type HIV-1 and mutant strains. The new DAPY analogue had lower cytotoxicity, higher selectivity index, and favorable pharmacokinetic properties, making it a potential candidate for HIV treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Yihui Song, Shu Wang, Min Zhao, Bin Yu
Summary: USP7, a deubiquitinating enzyme, is a promising therapeutic target. Through the development of a reliable fluorescence high-throughput screening method and the identification of potential ligandable pockets in the full length of USP7, we have enriched the toolbox for the discovery of potent and selective USP7 inhibitors.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Bin Yu, Junbiao Chang
Summary: Azvudine, a modified nucleoside, has been approved for the treatment of HIV-1 and COVID-19. It acts by inhibiting viral replication and has shown effectiveness in clinical trials. It has received conditional authorization in China and Russia.
CHINESE JOURNAL OF CHEMISTRY
(2023)
Editorial Material
Chemistry, Medicinal
Jingya Zhang, Wenshuo Gao, Yixia Wang, Junbiao Chang, Bin Yu
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Toxicology
Jialin Yuan, Ruiman Que, Weichao Zhao, Fengmei Song, Yi Cao, Bin Yu
Summary: In this study, the effects of two LSD1 inhibitors, ORY-1001 and 199, were compared on HUVECs in vitro and on zebrafish larvae in vivo. The results showed that both ORY-1001 and 199 had negligible effects on cell viability but significantly reduced the release of inflammatory cytokines and increased NO production. In zebrafish larvae, ORY-1001 treatment also affected blood flow and gene expression related to inflammation and vasculature function.
JOURNAL OF APPLIED TOXICOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Nan Wang, Ting Ma, Bin Yu
Summary: Drug resistance is a major cause of cancer recurrence and poor prognosis. Epigenetic regulation, which involves heritable changes in gene expression, is independent of changes in nucleotide sequences. Three common mechanisms of epigenetic regulation, DNA methylation, histone modification, and non-coding RNA regulation, have been extensively studied. Aberrant epigenetic regulation has been shown to contribute to tumor resistance, making targeting epigenetic regulators an effective strategy to reverse drug resistance. This review summarizes the roles of epigenetic regulation in tumor resistance and discusses the functions and regulatory mechanisms of histone demethylases, as well as therapeutic strategies for overcoming drug resistance.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)