☆ 4.7 Article

Discovery of 4-(dihydropyridinon-3-yl)amino-5-methylthieno[2,3-d]pyrimidine derivatives as potent Mnk inhibitors: synthesis, structure-activity relationship analysis and biological evaluation

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2015)

Journal

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Volume 95, Issue -, Pages 116-126

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

DOI: 10.1016/j.ejmech.2015.03.032

Keywords

eIF4E; Mnk; Inhibitor; Structure-activity relationship; Thieno[2,3-d]pyrimidine derivatives

Categories

Chemistry, Medicinal

Funding

Australia Government National Health and Medical Research Council [1050825]
South Australian Health and Medical Research Institute, Beat Cancer Project Principal Cancer Research Fellowship

Ask authors/readers for more resources

Protocol

Community support

Reagent

Community support

Abstract

Phosphorylation of the eukaryotic initiation factor 4E (eIF4E) by mitogen-activated protein kinase (MAPK)-interacting kinases (Mnks) is essential for oncogenesis but unnecessary for normal development. Thus, pharmacological inhibition of Mnks may offer an effective and non-toxic anti-cancer therapeutic strategy. Herein, we report the discovery of 4-(dihydropyridinon-3-yl)amino-5-methylthieno[2,3-d]pyrimidine derivatives as potent Mnk inhibitors. Docking study of 7a in Mnk2 suggests that the compound is stabilised in the ATP binding site through multiple hydrogen bonds and hydrophobic interaction. Cellular mechanistic studies on MV-4-11 cells with leads 7a, 8e and 8f reveal that they are able to down-regulate the phosphorylated eIF4E, Mcl-1 and cyclin D1, and induce apoptosis. (C) 2015 Elsevier Masson SAS. All rights reserved.

Authors

I am an author on this paper

Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7

Not enough ratings

Secondary Ratings

Novelty

-

Significance

-

Scientific rigor

-

Rate this paper

Recommended

Article Chemistry, Physical

Efficient synthesis and cytotoxic activity of polysubstituted thieno[2,3-d]pyrimidine derivatives

Tianshuai Wang, Fengxu Wu, Lun Luo, Yan Zhang, Junkai Ma, Yanggen Hu

Summary: The fused heterocyclic ring system of thienopyrimidine scaffold has been widely used in pharmaceuticals to enhance pharmacological and biological activities. In this study, polysubstituted thieno[2,3-d]pyrimidine derivatives were synthesized and tested for their cytotoxic activity against Hela and A549 cancer cell lines. Compound 8c showed promising activity similar to the lead drug Olmutinib, and its binding to EGFR kinase differed from Olmutinib. The preliminary structure-activity relationship suggested that introducing oxygen substituents favored antitumor activity.

JOURNAL OF MOLECULAR STRUCTURE (2022)

Add to Collection

Article Chemistry, Medicinal

Design, synthesis and antibacterial activity of novel pleuromutilin derivatives with thieno[2,3-d]pyrimidine substitution

Rongcai Ding, Xiaoxia Wang, Jianfang Fu, Yaoyao Chang, Yingxue Li, Yajing Liu, Yue Liu, Jinlong Ma, Jinxing Hu

Summary: A series of novel pleuromutilin derivatives with substituted thienopyrimidines were designed, synthesized, and evaluated for their antibacterial activity. Most of the compounds exhibited moderate antibacterial activity against Staphylococcus aureus, Streptococcus agalactiae, and Escherichia coli. Compound A11 showed the most activity and displayed bacteriostatic activities against methicillin-resistant S. aureus.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2022)

Add to Collection

Article Biochemistry & Molecular Biology

Design, synthesis, and biological evaluation of pyrido[2,3-d]pyrimidine and thieno[2,3-d]pyrimidine derivatives as novel EGFRL858R/T790M inhibitors

Jianfang Fu, Jie Yu, Xiang Zhang, Yaoyao Chang, Hongze Fan, Mengzhen Dong, Mengjia Li, Yue Liu, Jinxing Hu

Summary: In this study, two series of EGFR kinase inhibitors were designed and synthesised. Compound B1 showed selective inhibition against EGFR (L858R/T790M) with an IC50 value of 13 nM and a 76-fold selectivity for EGFR (WT). In vitro experiments demonstrated that compound B1 effectively inhibited proliferation of H1975 cells with an IC50 value of 0.087 μM. Mechanistic studies confirmed the selective inhibition of EGFR (L858R/T790M) by compound B1 through cell migration and apoptosis assays.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2023)

Add to Collection

Article Biochemistry & Molecular Biology

Discovery of new thieno[2,3-d]pyrimidine and thiazolo[5,4-d]pyrimidine derivatives as orally active phosphoinositide 3-kinase inhibitors

Yan Sun, Rong Fu, Songwen Lin, Jingbo Zhang, Ming Ji, Yan Zhang, Deyu Wu, Kehui Zhang, Hua Tian, Mingyi Zhang, Li Sheng, Yan Li, Jing Jin, Xiaoguang Chen, Heng Xu

Summary: A new series of PI3K inhibitors were designed and synthesized, showing promising anti-cancer activity and in vivo efficacy. Among them, thiazolo [5,4-d]pyrimidine 7a demonstrated superior anti-cancer activity compared to other compounds, warranting further pre-clinical evaluation.

BIOORGANIC & MEDICINAL CHEMISTRY (2021)

Add to Collection

Review Chemistry, Medicinal

MNK, mTOR or eIF4E-selecting the best anti-tumor target for blocking translation initiation

Shuo Li, Jia-shu Chen, Xiangqian Li, Xiaoyi Bai, Dayong Shi

Summary: Overexpression of eIF4E is common in various solid tumors and hematologic cancers, making it a potential anti-cancer target. This review provides a detailed classification and description of the anti-cancer activities of promising compounds, concluding that MNK1/2 and eIF4E/eIF4G interaction inhibitors are superior to mTOR inhibitors for targeted therapy.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2023)

Add to Collection

Article Chemistry, Medicinal

Discovery of Thieno[2,3-d]pyrimidine-based KRAS G 12D inhibitors as potential anticancer agents via combinatorial virtual screening

Ling Li, Jin Liu, Zichao Yang, Huiting Zhao, Bulian Deng, Yichang Ren, Ruiyao Mai, Junli Huang, Jianjun Chen

Summary: A series of novel thieno[2,3-d]pyrimidine analogs were designed and synthesized as KRAS G12D inhibitors. Compound KD-8 exhibited potent antiproliferative activity and antitumor efficacy by decreasing the active form of KRAS and inhibiting Raf and Erk in KRAS G12D mutated cancer cell lines.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2022)

Add to Collection

Article Chemistry, Physical

Design, synthesis, biological evaluation, and molecular docking of some new Thieno[2,3-d] pyrimidine derivatives

Mahmoud S. Tolba, Ahmed M. Sayed, Mostafa Sayed, Mostafa Ahmed

Summary: A synthetic method for designing new thienopyrimidines was presented, with spectral analysis confirming the structures of all synthesized compounds. The compounds showed significant antibacterial and anti-inflammatory activity compared to standard drugs, and molecular docking was used to investigate their mechanisms. Drug-like properties were analyzed for potential oral drug candidates.

JOURNAL OF MOLECULAR STRUCTURE (2021)

Add to Collection

Article Chemistry, Medicinal

Design, synthesis and anti-ovarian cancer activities of thieno[2,3-d] pyrimidine based chimeric BRD4 inhibitor/nitric oxide-donator

Yuehua Zhang, Zhaoping Pan, Can Chen, Yiwei Tan, Xiaoyun Wang, Lian Wang, Lu Zhang, Yi Chen, Gu He

Summary: By utilizing a multifunctional drug development strategy, new derivatives of BRD4 inhibitors capable of releasing nitric oxide were designed and synthesized, demonstrating excellent antitumor activity and inducing cellular apoptosis and autophagic cell death. This approach holds potential for targeted therapy in ovarian cancer.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2023)

Add to Collection

Article Chemistry, Medicinal

Discovery of Pyrrolo[2,3-d]pyrimidine derivatives as potent and selective colony stimulating factor 1 receptor kinase inhibitors

Xiaofei Liang, Chun Wang, Beilei Wang, Juan Liu, Shuang Qi, Aoli Wang, Qingwang Liu, Maoqing Deng, Li Wang, Jing Liu, Qingsong Liu

Summary: CSF1R kinase is crucial in tumor-associated macrophage repolarization, and the selective inhibitor 18h shows potent inhibition against CSF1R with significant selectivity, leading to suppression of tumor growth.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2022)

Add to Collection

Article Biochemistry & Molecular Biology

Discovery of thieno[2,3-d]pyrimidine-based derivatives as potent VEGFR-2 kinase inhibitors and anti-cancer agents

Souad A. El-Metwally, Mohsen M. Abou-El-Regal, Ibrahim H. Eissa, Ahmed B. M. Mehany, Hazem A. Mahdy, Hazem Elkady, Alaa Elwan, Eslam B. Elkaeed

Summary: Novel thieno[2,3-d]pyrimidine derivatives with structural similarity to VEGFR-2 inhibitors were designed and synthesized, showing promising anticancer activities against human cancer cell lines. Compound 17f exhibited the highest cytotoxic activities against HCT-116 and HepG2 cell lines and displayed high inhibitory activity against VEGFR-2, comparable to the reference drug sorafenib. ADMET and toxicity assessments revealed that most compounds had low BBB penetration levels and were non-toxic, except for compounds 17b and 20b.

BIOORGANIC CHEMISTRY (2021)

Add to Collection

Article Chemistry, Organic

Palladium-Catalyzed Highly Regioselective C6 Arylation of Pyrrolo[2,3-d]pyrimidine Derivatives with Arylboronic Acids

Min Liu, Chunwei Shen, Ting Tang, Chenhong Pan, Mingrui Liu, Xingxian Zhang

Summary: This article describes a mild and selective C6 arylation strategy for pyrrolo[2,3-d]pyrimidine derivatives using arylboronic acids at room temperature. The unified protocol combines Pd(II)/TEMPO catalysis and CF3CO2H promotion under silver-, base-, and additive-free conditions. The broad substrate scope, good functional group tolerance, excellent regioselectivity, and air and moisture tolerant conditions make this process attractive for the effective synthesis and modification of targeted small molecule drugs.

ORGANIC LETTERS (2023)

Add to Collection

Article Chemistry, Medicinal

Discovery of pyrrolo[2,3-d]pyrimidine derivatives as potent Axl inhibitors: Design, synthesis and biological evaluation

Dandan Xu, Deqiao Sun, Wei Wang, Xia Peng, Zhengsheng Zhan, Yinchun Ji, Yanyan Shen, Meiyu Geng, Jing Ai, Wenhu Duan

Summary: Axl has become an attractive target for cancer therapy due to its correlation with tumor growth, metastasis, poor survival, and drug resistance. Compound 13b, among the new Axl inhibitors studied, showed high enzymatic and cellular potencies and promising therapeutic effects in animal models, indicating its potential as a lead compound for new antitumor drug discovery.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

Add to Collection

Article Chemistry, Medicinal

Thieno[2,3-d]pyrimidine-Core Compounds Show Activity against Clinically Relevant Gram-Positive Bacteria

Olga Riabova, Anna Egorova, Alexander Lepioshkin, Yan Li, Kerstin Voigt, Florian Kloss, Vadim Makarov

Summary: Thieno[2,3-d]pyrimidines represent a novel antibacterial prodrug scaffold with potential antibacterial effects against Gram-positive bacteria, particularly Staphylococci (MRSA). The two most promising hit compounds demonstrate good pharmacokinetic properties in vitro and acceptable toxicity, qualifying them as starting points for lead-generation campaigns.

CHEMMEDCHEM (2022)

Add to Collection

Article Chemistry, Medicinal

Discovery of 7H-Pyrrolo[2,3-d]pyrimidine Derivatives as potent hematopoietic progenitor kinase 1 (HPK1) inhibitors

Feifei Wu, Huiyu Li, Qi An, Yaoliang Sun, Jinghua Yu, Wenting Cao, Pu Sun, Xingxing Diao, Linghua Meng, Shilin Xu

Summary: HPK1 is a potential therapeutic target for cancer immunotherapy as a negative regulator of TCR signaling. In this study, a series of HPK1 inhibitors with a 7H-pyrrolo[2,3-d]pyrimidine scaffold were designed and synthesized, among which compound 31 showed potent inhibitory activity and favorable selectivity. These findings provide new insights for further optimization and development of HPK1 inhibitors for cancer immunotherapy.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2023)

Add to Collection

Article Chemistry, Multidisciplinary

Synthesis, Antitumor Activity, and In Silico Drug Design of New Thieno[2,3-d]Pyrimidine-4-One Derivatives as Nonclassical Lipophilic Dihydrofolate Reductase Inhibitors

Ola A. Abdelaziz, Walaa M. El Husseiny, Khalid B. Selim, Hassan M. Eisa

Summary: A new series of compounds with the thieno[2,3-d]pyrimidine-4-one scaffold were synthesized and tested for their inhibitory activity against human tumor cell lines. Compounds 20 and 23 exhibited potent growth inhibitions and stronger inhibitory effects on dihydrofolate reductase compared to the standard antitumor agent 5-fluorouracil.

ACS OMEGA (2022)

Add to Collection

Review Pharmacology & Pharmacy

An overview of CDK3 in cancer: clinical significance and pharmacological implications

Theodosia Teo, Sara Kasirzadeh, Hugo Albrecht, Matthew J. Sykes, Yuchao Yang, Shudong Wang

Summary: CDK3 plays a significant role in the cell cycle and is involved in tumorigenesis and cell transformation. However, limited progress has been made in understanding its function due to the lack of selective pharmacological inhibitors.

PHARMACOLOGICAL RESEARCH (2022)

Add to Collection

Review Oncology

Using GPCRs as Molecular Beacons to Target Ovarian Cancer with Nanomedicines

Riya Khetan, Cintya Dharmayanti, Todd A. Gillam, Eric Kubler, Manuela Klingler-Hoffmann, Carmela Ricciardelli, Martin K. Oehler, Anton Blencowe, Sanjay Garg, Hugo Albrecht

Summary: This article reviews recent advancements in the targeted delivery of therapeutics to ovarian cancer using nanoparticles and explores the applicability of targeting highly expressed cell surface receptors in ovarian cancer tissue. Targeted nanomedicine strategies have the potential to increase drug accumulation in tumor cells, prevent adverse effects on healthy tissue, and lead to improved patient outcomes.

CANCERS (2022)

Add to Collection

Article Biochemistry & Molecular Biology

2-Anilino-4-(1-methyl-1H-pyrazol-4-yl)pyrimidine-derived CDK2 inhibitors as anticancer agents: Design, synthesis & evaluation

Biruk Sintayehu Fanta, Laychiluh Mekonnen, Sunita K. C. Basnet, Theodosia Teo, Jimma Lenjisa, Nishat Z. Khair, Lianmeng Kou, Solomon Tadesse, Matthew J. Sykes, Mingfeng Yu, Shudong Wang

Summary: CDK2 deregulation is associated with various human cancers and resistance to anticancer drugs. Bioisosteric replacement of CDKI-73 by a pyrazole group yielded compounds with potent CDK2 inhibition and antiproliferative activity against cancer cell lines. The results highlight the potential of the 2-anilino-4-(1-methyl-1H- pyrazol-4-yl)pyrimidine series in developing selective CDK2 inhibitors for cancer treatment.

BIOORGANIC & MEDICINAL CHEMISTRY (2023)

Add to Collection

Article Chemistry, Medicinal

Discovery of Potent Inhibitors of Cyclin-Dependent Kinases 7 and 9: Design, Synthesis, Structure-Activity Relationship Analysis and Biological Evaluation

Renjie Chen, Ramin Hassankhani, Yi Long, Sunita K. C. Basnet, Theodosia Teo, Yuchao Yang, Laychiluh Mekonnen, Mingfeng Yu, Shudong Wang

Summary: In this study, a series of N-pyridinylpyrimidin-2-amines were designed, synthesized, and evaluated, among which one compound was found to be the most potent inhibitor of CDKs 7 and 9 and the most effective anti-proliferative agent against multiple human cancer cell lines.

CHEMMEDCHEM (2023)

Add to Collection

Review Pharmacology & Pharmacy

Kinase inhibitors: Opportunities for small molecule anticancer immunotherapies

Ava Safaroghli-Azar, Fatemeh Emadi, Jimma Lenjisa, Laychiluh Mekonnen, Shudong Wang

Summary: As the fifth pillar of cancer treatment, immunotherapy has revolutionized therapeutic strategies by focusing on the host's immune system. The discovery of immune-modulatory effects for kinase inhibitors has opened up new possibilities in this approach, as these small molecule inhibitors not only directly target essential proteins for tumor survival and proliferation, but also stimulate immune responses against malignant cells.

DRUG DISCOVERY TODAY (2023)

Add to Collection

Article Biochemistry & Molecular Biology

Discovery of N,4-Di(1H-pyrazol-4-yl)pyrimidin-2-amine-Derived CDK2 Inhibitors as Potential Anticancer Agents: Design, Synthesis, and Evaluation

Biruk Sintayehu Fanta, Jimma Lenjisa, Theodosia Teo, Lianmeng Kou, Laychiluh Mekonnen, Yuchao Yang, Sunita K. C. Basnet, Ramin Hassankhani, Matthew J. Sykes, Mingfeng Yu, Shudong Wang

Summary: By bioisosteric replacement, a novel series of N,4-di(1H-pyrazol-4-yl)pyrimidin-2-amines were obtained as CDK2 inhibitors. Compound 15 exhibited the most potent CDK2 inhibitory activity with selectivity over other CDKs and showed sub-micromolar antiproliferative activity against cancer cells. This study highlights the potential of N,4-di(1H-pyrazol-4-yl)pyrimidin-2-amine scaffold as potent and selective CDK2 inhibitors for cancer treatment.

MOLECULES (2023)

Add to Collection

Article Oncology

Anti-Leukaemic Activity of Rilpivirine Is Mediated by Aurora A Kinase Inhibition

Saiful Islam, Muhammed H. H. Rahaman, Mingfeng Yu, Benjamin Noll, Jennifer H. H. Martin, Shudong Wang, Richard Head

Summary: Rilpivirine, an anti-viral drug, has been shown to inhibit the growth of leukemia cells and has potential as a treatment for acute myeloid leukemia (AML).

CANCERS (2023)

Add to Collection

Article Biochemistry & Molecular Biology

Selective inhibition of CDK9 in triple negative breast cancer

Ebtihal H. Mustafa, Geraldine Laven-Law, Zoya Kikhtyak, Van Nguyen, Simak Ali, Alex A. Pace, Richard Iggo, Alemwork Kebede, Ben Noll, Shudong Wang, Jean M. Winter, Amy R. Dwyer, Wayne D. Tilley, Theresa E. Hickey

Summary: Targeting transcription via CDK9 could be a potential therapeutic strategy for TNBC. Preclinical studies showed that a selective CDK9 inhibitor, CDDD11-8, effectively inhibited proliferation, induced cell cycle arrest, and increased apoptosis of TNBC cells in vitro and in vivo, without apparent toxicity to normal tissues.

ONCOGENE (2023)

Add to Collection

Article Chemistry, Medicinal

Highly potent dual-targeting angiotensin-converting enzyme 2 (ACE2) and Neuropilin-1 (NRP1) peptides: A promising broad-spectrum therapeutic strategy against SARS-CoV-2 infection

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)

Add to Collection

Article Chemistry, Medicinal

Discovery of proteolysis-targeting chimera targeting undruggable proteins using a covalent ligand screening approach

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)

Add to Collection

Article Chemistry, Medicinal

A pro-death autophagy-based nanoplatform for enhancing antitumour efficacy with improved immune responses

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)

Add to Collection

Article Chemistry, Medicinal

A novel scaffold long-acting selective estrogen receptor antagonist and degrader with superior preclinical profile against ER plus breast cancer

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)

Add to Collection

Article Chemistry, Medicinal

HDAC specificity and kinase off-targeting by purine-benzohydroxamate anti-hematological tumor agents

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)

Add to Collection

Article Chemistry, Medicinal

Unexpected rearrangement of ivermectin in the synthesis of new derivatives with trypanocidal and antiplasmodial activities

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)

Add to Collection

Article Chemistry, Medicinal

Novel ligustilide derivatives target quorum sensing system LasR/LasB and relieve inflammatory response against Pseudomonas aeruginosa infection

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)

Add to Collection

Article Chemistry, Medicinal

Design and synthesis of pterostilbene derivatives bearing triazole moiety that might treat DSS-induced colitis in mice through modulation of NF-KB/ MAPK signaling pathways

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)

Add to Collection

Article Chemistry, Medicinal

Discovery of 4-(N-dithiobenzyl piperazine)-1,8-naphthalimide as a potent multi-target antitumor agent with good efficacy, limited toxicity, and low resistance

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)

Add to Collection

© Peeref 2019-2024. All rights reserved.