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.

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

Probing benzenesulfonamide-thiazolidinone hybrids as multitarget directed ligands for efficient control of type 2 diabetes mellitus through targeting the enzymes: α-glucosidase and carbonic anhydrase II
Eur J Med Chem. 2024 Apr 20;271:116434. doi: 10.1016/j.ejmech.2024.116434. Online ahead of print.ABSTRACTDiabetes mellitus is a chronic metabolic disorder characterized by improper expression/function of a number of key enzymes that can be regarded as targets for anti-diabetic drug design. Herein, we report the design, synthesis, and biological assessment of two series of thiazolidinone-based sulfonamides 4a-l and 5a-c as multitarget directed ligands (MTDLs) with potential anti-diabetic activity through targeting the enzymes: α-glucosidase and human carbonic anhydrase (hCA) II. The synthesized sulfonamides were evaluated ...
Source: European Journal of Medicinal Chemistry - April 23, 2024 Category: Chemistry Authors: Mona A Gamal Samar H Fahim Simone Giovannuzzi Marwa A Fouad Alessandro Bonardi Paola Gratteri Claudiu T Supuran Ghaneya S Hassan Source Type: research

Benzothiazole derivatives as histone deacetylase inhibitors for the treatment of autosomal dominant polycystic kidney disease
Eur J Med Chem. 2024 Apr 18;271:116428. doi: 10.1016/j.ejmech.2024.116428. Online ahead of print.ABSTRACTRecent evidence suggests that histone deacetylases (HDACs) are important regulators of autosomal dominant polycystic kidney disease (ADPKD). In the present study, a series of benzothiazole-bearing compounds were designed and synthesized as potential HDAC inhibitors. Given the multiple participation of HDACs in ADPKD cyst progression, we embarked on a targeted screen using HeLa nuclear extracts to identify potent pan-HDAC inhibitors. Compound 26 emerged as the most efficacious candidate. Subsequent pharmacological charac...
Source: European Journal of Medicinal Chemistry - April 23, 2024 Category: Chemistry Authors: Xudong Cao Zhiyuan Fan Lingfang Xu Wenchao Zhao Haoran Zhang Yunfang Yang Ying Ren Yuxian Xiao Nan Zhou Long Yin Xueyan Zhou Xu Zhu Dong Guo Source Type: research

Research strategies of small molecules as chemotherapeutics to overcome multiple myeloma resistance
Eur J Med Chem. 2024 Apr 20;271:116435. doi: 10.1016/j.ejmech.2024.116435. Online ahead of print.ABSTRACTMultiple myeloma (MM), a cancer of plasma cells, is the second most common hematological malignancy which is characterized by aberrant plasma cells infiltration in the bone marrow and complex heterogeneous cytogenetic abnormalities. Over the past two decades, novel treatment strategies such as proteasome inhibitors, immunomodulators, and monoclonal antibodies have significantly improved the relative survival rate of MM patients. However, the development of drug resistance results in the majority of MM patients suffering...
Source: European Journal of Medicinal Chemistry - April 22, 2024 Category: Chemistry Authors: Jin Yang Yan-Cheng Yu Zi-Xuan Wang Qing-Qing Li Ning Ding Xue-Jiao Leng Jiao Cai Meng-Yuan Zhang Jing-Jing Wang Yun Zhou Tian-Hua Wei Xin Xue Wei-Chen Dai Shan-Liang Sun Ye Yang Nian-Guang Li Zhi-Hao Shi Source Type: research

Application of covalent modality in proximity-induced drug pharmacology: Early development, current strategy, and feature directions
Eur J Med Chem. 2024 Apr 17;271:116394. doi: 10.1016/j.ejmech.2024.116394. Online ahead of print.ABSTRACTWith a growing number of covalent drugs securing FDA approval as successful therapies across various indications, particularly in the realm of cancer treatment, the covalent modulating strategy is undergoing a resurgence. The renewed interest in covalent bioactive compounds has captured significant attention from both the academic and biopharmaceutical industry sectors. Covalent chemistry presents several advantages over traditional noncovalent proximity-induced drugs, including heightened potency, reduced molecular siz...
Source: European Journal of Medicinal Chemistry - April 21, 2024 Category: Chemistry Authors: Linjie Li Song Liu Youfu Luo Source Type: research

Synthesis of LAVR-289, a new [(Z)-3-(acetoxymethyl)-4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl]phosphonic acid prodrug with pronounced antiviral activity against DNA viruses
Eur J Med Chem. 2024 Apr 15;271:116412. doi: 10.1016/j.ejmech.2024.116412. Online ahead of print.ABSTRACTNew acyclic pyrimidine nucleoside phosphonate prodrugs with a 4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl]phosphonic acid skeleton (O-DAPy nucleobase) were prepared through a convergent synthesis by olefin cross-metathesis as the key step. Several acyclic nucleoside 4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl]phosphonic acid prodrug exhibited in vitro antiviral activity in submicromolar or nanomolar range against varicella zoster virus (VZV), human cytomegalovirus (HCMV), human herpes virus type 1 (HSV-1) and type 2 (HS...
Source: European Journal of Medicinal Chemistry - April 21, 2024 Category: Chemistry Authors: Maximes Bessi ères Vincent Roy Tuniyazi Abuduani Patrick Favetta Robert Snoeck Graciela Andrei Jennifer Moffat Franck Gallardo Luigi A Agrofoglio Source Type: research

Discovery of N-(4-((6-(3,5- Dimethoxyphenyl)-9H-purine derivatives as irreversible covalent FGFR inhibitors
Eur J Med Chem. 2024 Apr 17;271:116415. doi: 10.1016/j.ejmech.2024.116415. Online ahead of print.ABSTRACTFibroblast growth factor receptor (FGFR) is an attractive target for cancer therapy, but existing FGFR inhibitors appear to hardly meet the demand for clinical application. Herein, a number of irreversible covalent FGFR inhibitors were designed and synthesized by selecting several five- and six-membered azaheterocycles as parent scaffold with different substituents to take over the hydrophobic region in the active pocket of FGFR proteins. Among the resulting target compounds, III-30 showed the most potent effect on enzy...
Source: European Journal of Medicinal Chemistry - April 21, 2024 Category: Chemistry Authors: Yuanjiang Wang Yanchang Pan Zhaodan Lv Shaohua Gou Source Type: research

Privileged small molecules against neglected tropical diseases: A perspective from structure activity relationships
Eur J Med Chem. 2024 Apr 16;271:116396. doi: 10.1016/j.ejmech.2024.116396. Online ahead of print.ABSTRACTNeglected tropical diseases (NTDs) comprise diverse infections with more incidence in tropical/sub-tropical areas. In spite of preventive and therapeutic achievements, NTDs are yet serious threats to the public health. Epidemiological reports of world health organization (WHO) indicate that more than 1.5 billion people are afflicted with at least one NTD type. Among NTDs, leishmaniasis, chagas disease (CD) and human African trypanosomiasis (HAT) result in substantial morbidity and death, particularly within impoverished...
Source: European Journal of Medicinal Chemistry - April 21, 2024 Category: Chemistry Authors: J Abbasi Shiran B Kaboudin N Panahi N Razzaghi-Asl Source Type: research

Identification of CH < sub > 2 < /sub > -linked quinolone-aminopyrimidine hybrids as potent anti-MRSA agents: Low resistance potential and lack of cross-resistance with fluoroquinolone antibiotics
Eur J Med Chem. 2024 Apr 11;271:116399. doi: 10.1016/j.ejmech.2024.116399. Online ahead of print.ABSTRACTThe structural optimization of B14, an antibacterial agent we previously obtained, has led to the discovery of a new class of CH2-linked quinolone-aminopyrimidine hybrids with potent anti-MRSA activities. Surprisingly, the hybrids lacking a C-6 fluoro atom at the quinolone nucleus showed equal or even stronger anti-MRSA activities than their corresponding 6-fluoro counterparts, despite the well-established structure-activity relationships (SARs) indicating that the 6-fluoro substituent enhances the antibacterial activit...
Source: European Journal of Medicinal Chemistry - April 19, 2024 Category: Chemistry Authors: Hongxue Dai Yue Hu Yiwen Zhang Qi Zhu Tao Xu Peng Cui Renhua Fan Qiuqin He Source Type: research

Identification of a new bisindolinone arresting IGROV1 cells proliferation
Eur J Med Chem. 2024 Apr 2;271:116365. doi: 10.1016/j.ejmech.2024.116365. Online ahead of print.ABSTRACTIn an initial screening, a series of novel Knoevenagel adducts were submitted to the National Cancer Institute for evaluation of antitumor activity in human cell lines. In particular, compound 5f showed remarkable selectivity against IGROV1, an ovarian cancer cell line, without affecting healthy human fibroblast cells. Analyses of cytotoxicity, cell proliferation, cell migration, epigenetic changes, gene expression, and DNA damage were performed to obtain detailed information about its antitumor properties. Our results s...
Source: European Journal of Medicinal Chemistry - April 19, 2024 Category: Chemistry Authors: Rita Morigi Chiara Zalambani Giovanna Farruggia Laura Verardi Daniele Esposito Alberto Leoni Francesca Borsetti Manuela Voltattorni Laura Zambonin Luca Pincigher Natalia Calonghi Alessandra Locatelli Source Type: research

Structure optimizing of flavonoids against both MRSA and VRE
Eur J Med Chem. 2024 Apr 16;271:116401. doi: 10.1016/j.ejmech.2024.116401. Online ahead of print.ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) cause more than 100,000 deaths each year, which need efficient and non-resistant antibacterial agents. SAR analysis of 162 flavonoids from the plant in this paper suggested that lipophilic group at C-3 was crucial, and then 63 novel flavonoid derivatives were designed and total synthesized. Among them, the most promising K15 displayed potent bactericidal activity against clinically isolated MRSA and VRE (MICs = 0.25-1.00 μg/mL...
Source: European Journal of Medicinal Chemistry - April 19, 2024 Category: Chemistry Authors: Mei-Zhen Wei Yan-Yan Zhu Wen-Biao Zu Huan Wang Li-Yu Bai Zhong-Shun Zhou Yun-Li Zhao Zhao-Jie Wang Xiao-Dong Luo Source Type: research

Data-oriented protein kinase drug discovery
Eur J Med Chem. 2024 Apr 15;271:116413. doi: 10.1016/j.ejmech.2024.116413. Online ahead of print.ABSTRACTThe continued growth of data from biological screening and medicinal chemistry provides opportunities for data-driven experimental design and decision making in early-phase drug discovery. Approaches adopted from data science help to integrate internal and public domain data and extract knowledge from historical in-house data. Protein kinase (PK) drug discovery is an exemplary area where large amounts of data are accumulating, providing a valuable knowledge base for discovery projects. Herein, the evolution of PK drug d...
Source: European Journal of Medicinal Chemistry - April 18, 2024 Category: Chemistry Authors: Elena Xerxa J ürgen Bajorath Source Type: research