European Journal of Medicinal Chemistry This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

High affinity and low PARP-trapping benzimidazole derivatives as a potential warhead for PARP1 degraders
Eur J Med Chem. 2024 Apr 25;271:116405. doi: 10.1016/j.ejmech.2024.116405. Online ahead of print.ABSTRACTPARPi have been explored and applied in the treatment of various cancers with remarkable efficacy, especially BRCA1/2 mutated ovarian, breast, prostate, and pancreatic cancers. However, PARPi renders inevitable drug resistance and showed high toxicity because of PARP-Trapping with long-term clinic tracking. To overcome the drug resistance and the high toxicity of PARPi, many novel methods have been developed including PROTACs. Being an event-driven technology, PROTACs needs a high affinity, low toxicity warhead with no ...
Source: European Journal of Medicinal Chemistry - April 28, 2024 Category: Chemistry Authors: Xiaoyu Peng Yang Li Junfeng Qu Lizhi Jiang Kaiyue Wu Dan Liu Yuping Chen Junmei Peng Yu Guo Xuan Cao Source Type: research

Fluorine in the pharmaceutical industry: Synthetic approaches and application of clinically approved fluorine-enriched anti-infectious medications
Eur J Med Chem. 2024 Apr 26;271:116446. doi: 10.1016/j.ejmech.2024.116446. Online ahead of print.ABSTRACTThe strategic integration of fluorine atoms into anti-infectious agents has become a cornerstone in the field of medicinal chemistry, owing to the unique influence of fluorine on the chemical and biological properties of pharmaceuticals. This review examines the synthetic methodologies that enable the incorporation of fluorine into anti-infectious drugs, and the resultant clinical applications of these fluorine-enriched compounds. With a focus on clinically approved medications, the discussion extends to the molecular m...
Source: European Journal of Medicinal Chemistry - April 28, 2024 Category: Chemistry Authors: Zhen-Xi Niu Jing Hu Jin-Feng Sun Ya-Tao Wang Source Type: research

Structure-based drug design of DNA minor groove binders and evaluation of their antibacterial and anticancer properties
This study shed light on the mechanism of action of MGBs and revealed the important structural features for their antitumor and antibacterial activities, which are important to guide future development of MGB derivatives as novel antibacterial and anticancer agents.PMID:38678825 | DOI:10.1016/j.ejmech.2024.116440 (Source: European Journal of Medicinal Chemistry)
Source: European Journal of Medicinal Chemistry - April 28, 2024 Category: Chemistry Authors: Hasan Y Alniss Hadeel M Al-Jubeh Yousef A Msallam Ruqaiyyah Siddiqui Zinb Makhlouf Anil Ravi Rania Hamdy Sameh S M Soliman Naveed A Khan Source Type: research

Improving tumor sensitivity by the introduction of an ester chain to triaryl derivatives targeting PD-1/PD-L1
Eur J Med Chem. 2024 Apr 25;271:116433. doi: 10.1016/j.ejmech.2024.116433. Online ahead of print.ABSTRACTPD-1/PD-L1 pathway blockade is a promising immunotherapy for the treatment of cancer. In this manuscript, a series of triaryl compounds containing ester chains were designed and synthesized based on the pharmacophore studies of the lead BMS-1. After several SAR iterations, 22 showed the best biochemical activity binding to hPD-L1 with an IC50 of 1.21 nM in HTRF assay, and a KD value of 5.068 nM in SPR analysis. Cell-based experiments showed that 22 effectively promoted A549 cell death by restoring T-cell immune function...
Source: European Journal of Medicinal Chemistry - April 28, 2024 Category: Chemistry Authors: Yonglei Zhang Fucheng Yin Zhongwen Luo Shang Li Xinxin Li Siyuan Wan Yifan Chen Lingyi Kong Xiaobing Wang Source Type: research

Discovery of the small molecular inhibitors against sclerostin loop3 as potential anti-osteoporosis agents by structural based virtual screening and molecular design
Eur J Med Chem. 2024 Apr 16;271:116414. doi: 10.1016/j.ejmech.2024.116414. Online ahead of print.ABSTRACTSclerostin is a secreted glycoprotein that expresses predominantly in osteocytes and inhibits bone formation by antagonizing the Wnt/β-catenin signaling pathway, and the loop3 region of sclerostin has recently discovered as a novel therapeutic target for bone anabolic treatment without increasing cardiovascular risk. Herein, we used a structural based virtual screening to search for small molecular inhibitors selectively targeting sclerostin loop3. A novel natural product hit ZINC4228235 (THFA) was identified as the sc...
Source: European Journal of Medicinal Chemistry - April 27, 2024 Category: Chemistry Authors: Sifan Yu Weifeng Huang Hao Zhang Yinfeng Guo Baoting Zhang Ge Zhang Jinping Lei Source Type: research

Tetrahydropyridine LIMK inhibitors: Structure activity studies and biological characterization
Eur J Med Chem. 2024 Apr 9;271:116391. doi: 10.1016/j.ejmech.2024.116391. Online ahead of print.ABSTRACTLIM Kinases, LIMK1 and LIMK2, have become promising targets for the development of inhibitors with potential application for the treatment of several major diseases. LIMKs play crucial roles in cytoskeleton remodeling as downstream effectors of small G proteins of the Rho-GTPase family, and as major regulators of cofilin, an actin depolymerizing factor. In this article we describe the conception, synthesis, and biological evaluation of novel tetrahydropyridine pyrrolopyrimidine LIMK inhibitors. Homology models were first...
Source: European Journal of Medicinal Chemistry - April 26, 2024 Category: Chemistry Authors: Anthony Champir é Rayan Berabez Abdennour Braka Aur élie Cosson Justine Corret Caroline Girardin Amandine Serrano Samia Aci-S èche Pascal Bonnet B éatrice Josselin Pierre Brindeau Sandrine Ruchaud R émy Leguevel Deep Chatterjee Sebastian Mathea Stefa Source Type: research

Quinazolines annelated at the N(3)-C(4) bond: Synthesis and biological activity
Eur J Med Chem. 2024 Apr 18;271:116411. doi: 10.1016/j.ejmech.2024.116411. Online ahead of print.ABSTRACTThis review covers article and patent data obtained mostly within the period 2013-2023 on the synthesis and biological activity of quinazolines [c]-annelated by five- and six-membered heterocycles. Pyrazolo-, benzimidazo-, triazolo- and pyrimido- [c]quinazoline systems have shown multiple potential activities against numerous targets. We highlight that most research efforts are directed to design of anticancer and antibacterial agents of azolo[c]quinazoline nature. This review emphases both on the medicinal chemistry as...
Source: European Journal of Medicinal Chemistry - April 26, 2024 Category: Chemistry Authors: Emiliya V Nosova Galina N Lipunova Yulia V Permyakova Valery N Charushin Source Type: research

Design, synthesis, and biological evaluation of 3-phenyl substituted pyridine derivatives as potential dual inhibitors of XOR and URAT1
Eur J Med Chem. 2024 Apr 18;271:116407. doi: 10.1016/j.ejmech.2024.116407. Online ahead of print.ABSTRACTXanthine oxidoreductase (XOR) and uric acid transporter 1 (URAT1) are two most widely studied targets involved in production and reabsorption of uric acid, respectively. Marketed drugs almost target XOR or URAT1, but sometimes, single agents might not achieve aim of lowering uric acid to ideal value in clinic. Thus, therapeutic strategies of combining XOR inhibitors with uricosuric drugs were proposed and implemented. Based on our initial work of virtual screening, A and B were potential hits for dual-targeted inhibitor...
Source: European Journal of Medicinal Chemistry - April 25, 2024 Category: Chemistry Authors: Chao Yang Haojie Cai Xinying Zhu Lei Zhang Jing Li Source Type: research

Exploring the modulatory influence on the antimalarial activity of amodiaquine using scaffold hybridisation with ferrocene integration
Eur J Med Chem. 2024 Apr 16;271:116429. doi: 10.1016/j.ejmech.2024.116429. Online ahead of print.ABSTRACTAmodiaquine (AQ) is a potent antimalarial drug used in combination with artesunate as part of artemisinin-based combination therapies (ACTs) for malarial treatment. Due to the rising emergence of resistant malaria parasites, some of which have been reported for ACT, the usefulness of AQ as an efficacious therapeutic drug is threatened. Employing the organometallic hybridisation approach, which has been shown to restore the antimalarial activity of chloroquine in the form of an organometallic hybrid clinical candidate fe...
Source: European Journal of Medicinal Chemistry - April 25, 2024 Category: Chemistry Authors: Mziyanda Mbaba Taryn M Golding Reinner O Omondi Roxanne Mohunlal Timothy J Egan Janette Reader Lyn-Marie Birkholtz Gregory S Smith Source Type: research

Design, synthesis, and biological evaluation of some 2-(3-oxo-5,6-diphenyl-1,2,4-triazin-2(3H)-yl)-N-phenylacetamide hybrids as MTDLs for Alzheimer's disease therapy
Eur J Med Chem. 2024 Apr 16;271:116409. doi: 10.1016/j.ejmech.2024.116409. Online ahead of print.ABSTRACTInspite of established symptomatic relief drug targets, a multi targeting approach is highly in demand to cure Alzheimer's disease (AD). Simultaneous inhibition of cholinesterase (ChE), β secretase-1 (BACE-1) and Dyrk1A could be promising in complete cure of AD. A series of 18 diaryl triazine based molecular hybrids were successfully designed, synthesized, and tested for their hChE, hBACE-1, Dyrk1A and Aβ aggregation inhibitory potentials. Compounds S-11 and S-12 were the representative molecules amongst the series wi...
Source: European Journal of Medicinal Chemistry - April 25, 2024 Category: Chemistry Authors: Digambar Kumar Waiker Akash Verma T A Gajendra None Namrata Anima Roy Pradeep Kumar Surendra Kumar Trigun Saripella Srikrishna Sairam Krishnamurthy Vincent Jo Davisson Sushant Kumar Shrivastava Source Type: research

Discovery of novel ocotillol derivatives modulating glucocorticoid receptor/NF- κB signaling for the treatment of sepsis
Eur J Med Chem. 2024 Apr 23;271:116427. doi: 10.1016/j.ejmech.2024.116427. Online ahead of print.ABSTRACTGlucocorticoids (GCs) have been used in the treatment of sepsis because of their potent anti-inflammatory effects. However, their clinical efficacy against sepsis remains controversial because of glucocorticoid receptor (GR) downregulation and side effects. Herein, we designed and synthesized 30 ocotillol derivatives and evaluated their anti-inflammatory activities. Ocotillol 24(R/S) differential isomers were stereoselective in their pharmacological action. Specifically, 24(S) derivatives had better anti-inflammatory ac...
Source: European Journal of Medicinal Chemistry - April 24, 2024 Category: Chemistry Authors: Gongshan Ma Xiaojin Gao Xin Zhang Haixia Li Zhiyuan Geng Jing Gao Shuxin Yang Zhiruo Sun Yuqi Lin Xiaomei Wen Qingguo Meng Leiming Zhang Yi Bi Source Type: research

Identification of naphthalimide-derivatives as novel PBD-targeted polo-like kinase 1 inhibitors with efficacy in drug-resistant lung cancer cells
Eur J Med Chem. 2024 Apr 20;271:116416. doi: 10.1016/j.ejmech.2024.116416. Online ahead of print.ABSTRACTTargeting polo-box domain (PBD) small molecule for polo-like kinase 1 (PLK1) inhibition is a viable alternative to target kinase domain (KD), which could avoid pan-selectivity and dose-limiting toxicity of ATP-competitive inhibitors. However, their efficacy in these settings is still low and inaccessible to clinical requirement. Herein, we utilized a structure-based high-throughput virtual screen to find novel chemical scaffold capable of inhibiting PLK1 via targeting PBD and identified an initial hit molecule compound ...
Source: European Journal of Medicinal Chemistry - April 24, 2024 Category: Chemistry Authors: Pingping Li Yongkun Li Xuesong Ma Liangping Li Shulan Zeng Yan Peng Hong Liang Guohai Zhang Source Type: research