Review
Chemistry, Medicinal
Amanda Garrido, Gonzalo Vera, Pierre-Olivier Delaye, Cecile Enguehard-Gueiffier
Summary: Imidazo[1,2-b]pyridazine scaffold is an important category of heterocyclic nucleus that offers various bioactive molecules. This review provides an overview of the development of this framework in medicinal chemistry, guiding the search for novel imidazo[1,2-b]pyridazine compounds with enhanced pharmacological properties and efficacy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Chuchu Li, Yuqiao Han, Zhengyang Wang, Yanan Yu, Chen Wang, Ziwei Ren, Yanzhi Guo, Tong Zhu, XuWen Li, Suzhen Dong, Mingliang Ma
Summary: Compound 42 showed excellent dual PI3K/mTOR inhibitory activity, significant in vitro and in vivo anti-tumoral activities, good kinase selectivity, low hepatotoxicity, modest plasma clearance and acceptable oral bioavailability. It is a promising PI3K/mTOR targeted anti-cancer drug candidate.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Xiaofei Xiao, Yunsheng Xu, Xihua Yu, Yinbo Chen, Weiwei Zhao, Zhendong Xie, Xueyan Zhu, Hongjiang Xu, Yulei Yang, Peng Zhang
Summary: To develop ALK inhibitors that can overcome second-generation ALK-TKIs, 19 novel imidazo[1,2-b]pyridazine macrocyclic derivatives were designed, synthesized, and tested. Among them, O-10 showed the most effective enzymatic inhibitory activity, with IC50 values of 2.6, 6.4, and 23 nM for ALKWT, ALKG1202R, and ALKL1196M/G1202R, respectively. O-10 also exhibited significant growth inhibition against ALK-positive cell lines, with IC50 values of 38, 52, and 64 nM for Karpas299, BaF3-EML4ALKG1202R, and BaF3-EML4-ALKL1196M/G1202R, respectively. Further evaluation of O-10's kinase selectivity, liver microsome stability, and in vivo pharmacokinetic properties was conducted, confirming its potential as an effective ALK inhibitor for various mutations.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Medicine, Research & Experimental
Tony Eight Lin, Min-Wu Chao, Wei-Chun HuangFu, Huang-Ju Tu, Zhao-Xiang Peng, Chih-Jou Su, Tzu-Ying Sung, Jui-Hua Hsieh, Cheng-Chung Lee, Chia-Ron Yang, Shiow-Lin Pan, Kai-Cheng Hsu
Summary: DYRK1A dysregulation is linked to various diseases, including neurodegenerative diseases like Alzheimer's. A novel selective small-molecule inhibitor targeting DYRK1A was identified through structure-based virtual screening, showing potential for alleviating tau protein aggregation in neurodegenerative pathologies.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Chemistry, Multidisciplinary
Ahmed El Akkaoui, Jamal Koubachi, Gerald Guillaumet, Said El Kazzouli
Summary: This review surveys recent developments in organometallic-chemistry-based methods for preparing and functionalizing imidazo[1,2-b]pyridazines, highlighting advances in C-H activation, N-arylation, and sequential couplings for these heterocyclic systems. This review does not include procedures involving metal-based catalysis.
Article
Chemistry, Medicinal
Josef Jansa, Radek Jorda, Jana Skerlova, Petr Pachl, Miroslav Perina, Eva Reznickova, Tomas Heger, Tomas Gucky, Pavlina Rezacova, Antonin Lycka, Vladimir Krystof
Summary: This study presents a series of substituted imidazo[1,2-c]pyrimidines as inhibitors of cyclin-dependent kinase 2 (CDK2), synthesized using various methods including Suzuki-Miyaura cross-coupling and halogenation. The compounds exhibited micro-to submicromolar inhibition of CDK2/cyclin E activity, with one compound showing strong binding to CDK2 and high selectivity against leukemia cell lines. This research suggests the potential of substituted imidazo[1,2-c]pyrimidines for future kinase inhibitor development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Petra Brehova, Eva Reznickova, Krystof Skach, Radek Jorda, Milan Dejmek, Veronika Vojackova, Michal Sala, Marketa Kovalova, Martin Dracinsky, Alexandra Dolnikova, Timotej Strmen, Monika Kinnertova, Karel Chalupsky, Alexandra Dvorakova, Tomas Gucky, Helena Mertlikova Kaiserova, Pavel Klener, Radim Nencka, Vladimir Krystoy
Summary: FLT3 kinase is a potential drug target in acute myeloid leukemia (AML), and this study investigates the suitability of various heterocycles as central cores of FLT3 inhibitors. Imidazo[1,2-b]pyridazines show high potency against FLT3. Compound 34f exhibits nanomolar inhibitory activity against FLT3 and suppresses FLT3 downstream signaling pathways. Moreover, it significantly blocks tumor growth in an AML mouse model.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Ravinder Kumar, Rahul Singh, Ayla das Chagas Almeida, Juliana da Trindade Granato, Ari Sergio de Oliveira Lemos, Kushvinder Kumar, Madhuri T. Patil, Adilson D. da Silva, Ambadas B. Rode, Elaine S. Coimbra, Deepak B. Salunke
Summary: Leishmania poses a substantial threat to the human population and the current drugs against it have limitations. Developing new drugs is crucial, and a library of imidazo-fused heterocycles was synthesized and screened. Compound 24 showed the strongest antileishmanial activity, with selectivity for a stage related to human disease. It was also more destructive to the parasites than host cells. These findings support the potential of imidazo-pyrimidine as a new antileishmanial pharmacophore and encourage further animal studies.
Article
Biochemistry & Molecular Biology
Rawan M. Sbenati, Mohammad H. Semreen, Ahlam M. Semreen, Mahmoud K. Shehata, Fai M. Alsaghir, Mohammed El-Gamal
Summary: This article reviewed the potential anticancer properties of imidazo[2,1-b]thiazole derivatives, focusing on their biological characteristics and structure-activity relationship (SAR). Reports published in the literature from 2011 to 2020 were the main focus of this review.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Plant Sciences
Miri Choi, Ae-kyeong Kim, Youngwook Ham, Joo-Youn Lee, Daeyong Kim, Ansook Yang, Min Ju Jo, Eunyoung Yoon, Jung-Nyoung Heo, Sang-Bae Han, Min-Hyo Ki, Kyu-Sun Lee, Sungchan Cho
Summary: Aristolactam BIII, a natural product derived from herbal plants, was identified as a novel DYRK1A inhibitor with therapeutic potential for DS-related pathological conditions.
Article
Chemistry, Medicinal
Sona Krajcovicova, Radek Jorda, David Vanda, Miroslav Soural, Vladimir Krystof
Summary: An efficient synthetic approach for trisubstituted imidazo [4,5-c]pyridines as BTK inhibitors was reported, with high tolerance of C6 substitutions observed. Cellular experiments indicated selective BTK targeting, suggesting the inhibitors could be potential options after ibrutinib failure.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Bangfu Zhu, Tom Parsons, Wenche Stensen, John S. Mjoen Svendsen, Anders Fugelli, James J. L. Hodge
Summary: Alzheimer's disease (AD) is a common neurodegenerative disease with no effective treatments. People with Down syndrome (DS) have an increased risk of AD, and DYRK1A may be a potential therapeutic target. Through studying Drosophila models, it was found that the DYRK1A inhibitor PST-001 can improve the pathological processes caused by AD and DS-associated genes.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Bangfu Zhu, Tom Parsons, Wenche Stensen, John S. Mjoen Svendsen, Anders Fugelli, James J. L. Hodge
Summary: Alzheimer's disease, a common neurodegenerative disease with no cure, is more prevalent in Down syndrome patients due to potential genetic factors. Research has shown that targeting DYRK1A gene with medication can reduce neurodegeneration caused by AD and DS-related genes.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Agata Barzowska, Barbara Pucelik, Katarzyna Pustelny, Alex Matsuda, Alicja Martyniak, Jacek Stepniewski, Anna Maksymiuk, Maciej Dawidowski, Ulli Rothweiler, Jozef Dulak, Grzegorz Dubin, Anna Czarna
Summary: This study demonstrates the efficacy of a set of small molecule inhibitors of DYRK1A kinase in promoting beta-cell proliferation, enhancing long-term insulin secretion, and balancing glucagon level in human islets. The compounds show significantly more pronounced effects compared to harmine and hold considerable promise for regenerative medicine in the treatment of T1DM and T2DM.
Article
Biochemistry & Molecular Biology
Rongrong Su, Yanyan Diao, Wenjie Sha, Dou Dou, Zhixiao Yu, Limin Leng, Zhenjiang Zhao, Zhuo Chen, Honglin Li, Yufang Xu
Summary: This study developed selective non-covalent BTK inhibitors by scaffold hopping and found that compound 2 and 4 exhibited high BTK inhibition potency. These compounds showed great ability to inhibit tumor growth in cell and animal models.
BIOORGANIC CHEMISTRY
(2022)
Article
Respiratory System
Laurent Meijer, Genevieve Hery-Arnaud, Cyril Leven, Emmanuel Nowak, Sophie Hillion, Yves Renaudineau, Isabelle Durieu, Raphael Chiron, Anne Prevotat, Isabelle Fajac, Dominique Hubert, Marlene Murris-Espin, Sandrine Huge, Isabelle Danner-Boucher, Bruno Ravoninjatovo, Sylvie Leroy, Julie Macey, Thierry Urban, Gilles Rault, Dominique Mottier, Rozenn Le Berre
Summary: A study was conducted to evaluate the safety and effects of roscovitine in patients with Cushing disease. The results showed that roscovitine was relatively safe and well-tolerated, but did not show significant efficacy in treating the disease. The variability in pharmacokinetics of roscovitine may have contributed to the lack of effectiveness.
JOURNAL OF CYSTIC FIBROSIS
(2022)
Article
Chemistry, Medicinal
Tania Tahtouh, Emilie Durieu, Benoit Villiers, Celine Bruyere, Thu Lan Nguyen, Xavier Fant, Kwang H. Ahn, Leepakshi Khurana, Emmanuel Deau, Mattias F. Lindberg, Elodie Severe, Frederic Miege, Didier Roche, Emmanuelle Limanton, Jean-Martial L'helgoual'ch, Guillaume Burgy, Solene Guiheneuf, Yann Herault, Debra A. Kendall, Francois Carreaux, Jean-Pierre Bazureau, Laurent Meijer
Summary: Leucettines, derived from marine sponge alkaloid Leucettamine B, have potential therapeutic applications for Alzheimer's disease, Down syndrome, diabetes, and other diseases. There is a correlation between the inhibition of specific kinase targets and cellular effects.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Clinical Neurology
B. Souchet, M. Audrain, Y. Gu, M. F. Lindberg, N. S. Orefice, E. Rey, N. Cartier, N. Janel, L. Meijer, Jerome Braudeau
Summary: The presence of both soluble forms of Aβ 342 and p-tau may be responsible for the onset of mild cognitive impairment (MCI) in Alzheimer's disease (AD).
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2022)
Article
Endocrinology & Metabolism
Mythily Ganapathi, Gaelle Friocourt, Naig Gueguen, Marisa W. Friederich, Gerald Le Gac, Volkan Okur, Nadege Loaec, Thomas Ludwig, Chandran Ka, Kurenai Tanji, Pascale Marcorelles, Evangelos Theodorou, Angela Lignelli-Dipple, Cecile Voisset, Melissa A. Walker, Lauren C. Briere, Amelie Bourhis, Marc Blondel, Charles LeDuc, Jacob Hagen, Cathleen Cooper, Colleen Muraresku, Claude Ferec, Armelle Garenne, Servane Lelez-Soquet, Cassandra A. Rogers, Yufeng Shen, Dana K. Strode, Peyman Bizargity, Alejandro Iglesias, Amy Goldstein, Frances A. High, David A. Sweetser, Rebecca Ganetzky, Johan L. K. Van Hove, Vincent Procaccio, Cedric Le Marechal, Wendy K. Chung
Summary: Mitochondrial complex V is important for oxidative phosphorylation and a rare variant in ATP5PO gene is associated with a severe multi-systemic disorder consistent with Leigh syndrome.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Review
Parasitology
Herve Lecoeur, Eric Prina, Maria Gutierrez-Sanchez, Gerald F. Spaeth
Summary: Intracellular parasites have evolved complex strategies to disrupt host cell functions and ensure their own survival. Leishmania parasites, in particular, cause severe immunopathologies by thriving inside immune cells. While the impact of Leishmania infection on host cell phenotype and functions has been studied, the regulatory mechanisms underlying host cell subversion were only recently investigated.
TRENDS IN PARASITOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Pierre Conan, Alice Leon, Mathilde Gourdel, Claire Rollet, Loubna Chair, Noeline Caroff, Nelig Le Goux, Catherine Le Jossic-Corcos, Maha Sinane, Lucile Gentile, Louise Maillebouis, Nadege Loaec, Jennifer Martin, Marie Vilaire, Laurent Corcos, Olivier Mignen, Mikael Croyal, Cecile Voisset, Frederic Bihel, Gaelle Friocourt
Summary: By using a yeast-based screening method, researchers have identified three new potent inhibitors of CBS. They also discovered the importance of copper and zinc levels in regulating the enzymatic activity of CBS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Priyanka Gupta, Keehn Strange, Rahul Telange, Ailan Guo, Heather Hatch, Amin Sobh, Jonathan Elie, Angela M. Carter, John Totenhagen, Chunfeng Tan, Yogesh A. Sonawane, Jiri Neuzil, Amarnath Natarajan, Ashley J. Ovens, Jonathan S. Oakhill, Thorsten Wiederhold, Karel Pacak, Hans K. Ghayee, Laurent Meijer, Sushanth Reddy, James A. Bibb
Summary: Metabolic dysfunction mutations can lead to cancer. Loss of SDHB triggers a signaling cascade that disrupts energy sensing and promotes cancer progression.
Review
Biochemistry & Molecular Biology
Yashoda Krishna Sunkari, Laurent Meijer, Marc Flajolet
Summary: Protein kinases are essential in biology and their deregulation is linked to various diseases. However, the high conservation of ATP-binding sites among kinases makes it challenging to develop highly specific inhibitors. In the context of neurodegenerative diseases, CK1 and other kinases have been implicated. Currently, there are no specific regulators for CK1, and known inhibitors target the ATP-binding site. DNA-encoded library technology may be a promising approach to discover allosteric modulators instead of ATP competitors.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Gaelle Angrand, Alicia Quillevere, Nadege Loaec, Van-Trang Dinh, Ronan Le Senechal, Rahima Chennoufi, Patricia Duchambon, Marc Keruzore, Rodrigo Prado Martins, Marie-Paule Teulade-Fichou, Robin Fahraeus, Marc Blondel
Summary: This study identifies type I arginine methyltransferases as therapeutic targets to interfere with EBNA1 and EBV immune evasion, providing evidence that interfering with GAr-based inhibition of translation is an important step to trigger an immune response against EBV-carrying cancers.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Medicinal
Mattias F. Lindberg, Emmanuel Deau, Jonas Arfwedson, Nicolas George, Pascal George, Patricia Alfonso, Ana Corrionero, Laurent Meijer
Summary: This study evaluates the kinase inhibitory activity of a library of DYRKs/CLKs inhibitors and finds a diverse range of potencies and selectivities among these inhibitors, highlighting the challenges of targeting kinases in this area of research. The use of a panel of inhibitors is suggested for studying the functions of these kinases in cellular processes.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Giovanni Bussotti, Blaise Li, Pascale Pescher, Barbora Vojtkova, Isabelle Louradour, Katerina Pruzinova, Jovana Sadlova, Petr Volf, Gerald F. Spath
Summary: This study investigates the genomic adaptation of the parasitic pathogen Leishmania donovani during sand fly infection. The findings suggest that oxidative DNA damage and DNA repair processes contribute to haplotype and allelic selection in the parasite.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Medicinal
Emmanuel Deau, Mattias F. F. Lindberg, Freideiric Miege, Didier Roche, Nicolas George, Pascal George, Andreas Kra''mer, Stefan Knapp, Laurent Meijer
Summary: Dual-specificity,tyrosine phosphorylation-regulated kinases (DYRKs) and cdc2-like kinases (CLKs) have been identified as important targets for various pathologies. In this study, a family of DYRK/CLK inhibitors called Leucettinibs, derived from Leucettines and Leucettamine B, were synthesized and characterized. These inhibitors showed subnanomolar IC50 on DYRK1A and demonstrated potential for therapeutic drug development. Kinase-inactive isomers, iso-Leucettinibs, were also synthesized as suitable negative control compounds. Leucettinibs were found to inhibit DYRK1A substrate phosphorylation in cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ronan Le Senechal, Marc Keruzore, Alicia Quillevere, Nadege Loaec, Van-Trang Dinh, Oksana Reznichenko, Pedro Guixens-Gallardo, Laurent Corcos, Marie-Paule Teulade-Fichou, Anton Granzhan, Marc Blondel
Summary: BCL-x is a master regulator of apoptosis and its alternative splicing is controlled by RBM25. RBM25 directly binds to an RNA G-quadruplex near the alternative splice site of BCL-x pre-mRNA, promoting the production of the pro-apoptotic Bcl-xS isoform. PhenDC3 and two newly discovered compounds, PhenDH8 and PhenDH9, enhance the binding of RBM25 to the G-quadruplex, thereby promoting apoptosis. This study highlights the importance of the RBM25/G-quadruplex interaction in sensitizing cancer cells to chemotherapy.
NUCLEIC ACIDS RESEARCH
(2023)
Correction
Clinical Neurology
B. Souchet, M. Audrain, Y. Gu, M. F. Lindberg, N. S. Orefice, E. Rey, N. Cartier, N. Janel, L. Meijer, Jerome Braudeau
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2023)
Correction
Geriatrics & Gerontology
B. Souchet, M. Audrain, Y. Gu, M. F. Lindberg, N. S. Orefice, E. Rey, N. Cartier, N. Janel, L. Meijer, Jerome Braudeau
JOURNAL OF NUTRITION HEALTH & AGING
(2022)
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)