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.

Development of benzimidazole-based compounds as novel capsid assembly modulators for the treatment of HBV infection
In this study, the hit compound CDI (IC50 = 2.46 ± 0.33 μM) was identified by screening of an in-house compound library. And then novel potent benzimidazole derivatives were designed and synthesized as core assembly modulators, and their antiviral effects were evaluated in vitro and in vivo biological experiments. The results indicated that compound 26f displayed the most optimized modulator of HBV capsid assembly (IC50 = 0.51 ± 0.20 μM, EC50 = 2.24 ± 0.43 μM, CC50 = 84.29 μM) and high selectivity index. Moreover, treatment with compound 26f for 14 days significantly decreased serum levels of HBV DNA levels in the H...
Source: European Journal of Medicinal Chemistry - April 18, 2024 Category: Chemistry Authors: Kaixin Du Xianyang Wang Yuxin Bai Xue Zhang Jie Xue Shanshan Li Youhua Xie Zhipei Sang Yu Tang Xin Wang Source Type: research

Design, synthesis, and biological evaluation of novel benzimidazole derivatives as anti-cervical cancer agents through PI3K/Akt/mTOR pathway and tubulin inhibition
In this study, we designed and synthesized a series of benzimidazole derivatives and evaluated their anti-cervical cancer activity. Compound 4r exhibited strong antiproliferative activity in different cervical cancer cell lines HeLa, SiHa and Ca Ski, and relative lower cytotoxicity to normal hepatic and renal cell lines LO2 and HEK-293t (IC50 values were at 21.08 μM and 23.96 μM respectively). Its IC50 value was at 3.38 μM to the SiHa cells. Further mechanistic studies revealed that 4r induced apoptosis, arrested cell cycle in G2/M phase, suppressed PI3K/Akt/mTOR pathway and inhibit the polymerization of tubulin. Molecu...
Source: European Journal of Medicinal Chemistry - April 18, 2024 Category: Chemistry Authors: Si-Si Li Jun-Jie Chen Miao-Miao Zhang Wei-Xu Wang Wei-Yi Zhang Cheng Ma Source Type: research

Discovery and optimization of narrow spectrum inhibitors of Tousled like kinase 2 (TLK2) using quantitative structure activity relationships
Eur J Med Chem. 2024 Apr 2;271:116357. doi: 10.1016/j.ejmech.2024.116357. Online ahead of print.ABSTRACTThe oxindole scaffold has been the center of several kinase drug discovery programs, some of which have led to approved medicines. A series of two oxindole matched pairs from the literature were identified where TLK2 was potently inhibited as an off-target kinase. The oxindole has long been considered a promiscuous kinase inhibitor template, but across these four specific literature oxindoles TLK2 activity was consistent, while the kinome profile was radically different ranging from narrow to broad spectrum kinome covera...
Source: European Journal of Medicinal Chemistry - April 18, 2024 Category: Chemistry Authors: Christopher R M Asquith Michael P East Tuomo Laitinen Carla Alamillo-Ferrer Erkka Hartikainen Carrow I Wells Alison D Axtman David H Drewry Graham J Tizzard Antti Poso Timothy M Willson Gary L Johnson Source Type: research

Quantum chemistry calculation-aided discovery of potent small-molecule mimics of glutathione peroxidases for the treatment of cisplatin-induced hearing loss
In this study, we employed the frontier molecular orbital (FMO) theory approach as a convenient prediction method for the glutathione peroxidase (GPx)-like activity of isoselenazolones and discovered new isoselenazolones with great GPx-like activity. Notably, compound 19 exhibited significant protective effects against cisplatin-induced hair cell (HC) damage in vitro and in vivo and effectively reverses cisplatin-induced hearing loss through oral administration. Further investigations revealed that this compound effectively alleviated hair cell oxidative stress, apoptosis and ferroptosis. This research highlights the poten...
Source: European Journal of Medicinal Chemistry - April 17, 2024 Category: Chemistry Authors: Wentao Wang Siyu Qiu Tianyi Zhang Zhiwei Zheng Kongkai Zhu Xing Gao Fengping Zhao Xinyuan Ma Hongyan Lin Yingzi He Canhui Zheng Source Type: research

Exploration of isoxazole analogs: Synthesis, COX inhibition, anticancer screening, 3D multicellular tumor spheroids, and molecular modeling
In this study, a new series of Isoxazole-carboxamide derivatives were synthesized and characterized via HRMS, 1H-, 13CAPT-NMR, and MicroED. The findings revealed that nearly all of the synthesized derivatives exhibited potent inhibitory activities against both COX enzymes, with IC50 values ranging from 4.1 nM to 3.87 μM. Specifically, MYM1 demonstrated the highest efficacy among the compounds tested against the COX-1, displaying an IC50 value of 4.1 nM. The results showed that 5 compounds possess high COX-2 isozyme inhibitory effects with IC50 value in range 0.24-1.30 μM with COX-2 selectivity indexes (2.51-6.13), among ...
Source: European Journal of Medicinal Chemistry - April 16, 2024 Category: Chemistry Authors: Mohammed Hawash Samer Abdallah Mahmoud Abudayyak Yarob Melhem Mohammed Abu Shamat Meera Aghbar Irfan Çapan Murad Abualhasan Anil Kumar Micha ł Kamiński Tomasz G óral Paulina Maria Dominiak Shorooq Sobuh Source Type: research

Design, synthesis and evaluation of a pyrazolo[3,4-d]pyrimidine derivative as a novel and potent TGF β1R1 inhibitor
In this study, we utilized an alternative conformation-similarity-based virtual screening (CSVS) combined with a fragment-based drug designing (FBDD) strategy to efficiently discover a potent and active hit with a novel chemical scaffold. After structural optimization in the principle of group replacement, compound 57 was identified as the most promising ALK5 inhibitor. Compound 57 demonstrated significant inhibitory effects against the TGF-β1/SMAD signaling pathway. It could markedly attenuate the production of extracellular matrix (ECM) and deposition of collagen. Also, the lead compound showed adequate pharmacokinetic ...
Source: European Journal of Medicinal Chemistry - April 16, 2024 Category: Chemistry Authors: Yubo Wang Yulin Liu Yan Zhang Zixuan Zhang Lei Xu Jiefu Wang Yijie Yang Biyu Hu Yuhong Yao Mingming Wei Junfeng Wang Bencan Tang Kun Zhang Shuangwei Liu Guang Yang Source Type: research

Novel selective agents for the degradation of AR/AR-V7 to treat advanced prostate cancer
Eur J Med Chem. 2024 Apr 15;271:116400. doi: 10.1016/j.ejmech.2024.116400. Online ahead of print.ABSTRACTThe androgen receptor AR antagonists, such as enzalutamide and apalutamide, are efficient therapeutics for the treatment of prostate cancer (PCa). Even though they are effective at first, resistance to both drugs occurs frequently. Resistance is mainly driven by aberrations of the AR signaling pathway including AR gene amplification and the expression of AR splice variants (e.g. AR-V7). This highlights the urgent need for alternative therapeutic strategies. Here, a total of 24 compounds were synthesized and biologically...
Source: European Journal of Medicinal Chemistry - April 16, 2024 Category: Chemistry Authors: Yifei Yang Guangyao Lv Ruijuan Xiu Huijie Yang Wenyan Wang Pengfei Yu Jianzhao Zhang Liang Ye Hongbo Wang Jingwei Tian Source Type: research

Modulators for palmitoylation of proteins and small molecules
Eur J Med Chem. 2024 Apr 12;271:116408. doi: 10.1016/j.ejmech.2024.116408. Online ahead of print.ABSTRACTAs an essential form of lipid modification for maintaining vital cellular functions, palmitoylation plays an important role in in the regulation of various physiological processes, serving as a promising therapeutic target for diseases like cancer and neurological disorders. Ongoing research has revealed that palmitoylation can be categorized into three distinct types: N-palmitoylation, O-palmitoylation and S-palmitoylation. Herein this paper provides an overview of the regulatory enzymes involved in palmitoylation, inc...
Source: European Journal of Medicinal Chemistry - April 15, 2024 Category: Chemistry Authors: Zeshuai Fan Yuchen Hao Yidan Huo Fei Cao Longfei Li Jianmei Xu Yali Song Kan Yang Source Type: research

Discovery of novel amide derivatives as potent quorum sensing inhibitors of Pseudomonas aeruginosa
In conclusion, amide derivatives A9 and B6 exhibit promising potential for further development as novel QS inhibitors in P. aeruginosa.PMID:38615409 | DOI:10.1016/j.ejmech.2024.116410 (Source: European Journal of Medicinal Chemistry)
Source: European Journal of Medicinal Chemistry - April 14, 2024 Category: Chemistry Authors: Zhe He Ming-Ming Guan Lan-Tu Xiong Xuan Li Yan Zeng Xile Deng Alastair N Herron Zi-Ning Cui Source Type: research

8-Bicycloalkyl-CPFPX derivatives as potent and selective tools for in vivo imaging of the A < sub > 1 < /sub > adenosine receptor
Eur J Med Chem. 2024 Apr 6;271:116380. doi: 10.1016/j.ejmech.2024.116380. Online ahead of print.ABSTRACTImaging of the A1 adenosine receptor (A1R) by positron emission tomography (PET) with 8-cyclopentyl-3-(3-[18F]fluoropropyl)-1-propyl-xanthine ([18F]CPFPX) has been widely used in preclinical and clinical studies. However, this radioligand suffers from rapid peripheral metabolism and subsequent accumulation of radiometabolites in the vascular compartment. In the present work, we prepared four derivatives of CPFPX by replacement of the cyclopentyl group with norbornane moieties. These derivatives were evaluated by competit...
Source: European Journal of Medicinal Chemistry - April 14, 2024 Category: Chemistry Authors: Swen Humpert Daniela Schneider Dirk Bier Annette Schulze Felix Neumaier Bernd Neumaier Marcus Holschbach Source Type: research