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.

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

Design, synthesis, and biological activity of D-bishomo-1 α,25-dihydroxyvitamin D < sub > 3 < /sub > analogs and their crystal structures with the vitamin D nuclear receptor
In this study, we present the synthesis of vitamin D derivatives characterized by an enlarged (seven-membered) ring D. Preparation of the designed vitamin D compounds required separate syntheses of crucial building blocks (C/D-rings fragments with side chain and rings A) which were combined by different methods, including Wittig-Horner reaction and Suzuki coupling. Biological activities of the target vitamin D analogs were assessed both in vitro and in vivo, demonstrating their significant potency compared to the natural hormone. Furthermore, the successful crystallization of these compounds with the vitamin D receptor (VD...
Source: European Journal of Medicinal Chemistry - April 14, 2024 Category: Chemistry Authors: Adrian Fabisiak Pawel Brzeminski Rafal R Sicinski Natacha Rochel Ewa Maj Beata Filip-Psurska Joanna Wietrzyk Lori A Plum Hector F DeLuca Source Type: research

Quinoxaline derivatives: Recent discoveries and development strategies towards anticancer agents
Eur J Med Chem. 2024 Apr 7;271:116360. doi: 10.1016/j.ejmech.2024.116360. Online ahead of print.ABSTRACTCancer is a leading cause of death and a major health problem worldwide. While many effective anticancer agents are available, most drugs currently on the market are not specific, raising issues like the common side effects of chemotherapy. However, recent research hold promises for the development of more efficient and safer anticancer drugs. Quinoxaline and its derivatives are becoming recognized as a novel class of chemotherapeutic agents with activity against different tumors. The present review compiles and discusse...
Source: European Journal of Medicinal Chemistry - April 13, 2024 Category: Chemistry Authors: Vincent Montero Marc Montana Manon Carr é Patrice Vanelle Source Type: research

Research progress of fullerenes and their derivatives in the field of PDT
Eur J Med Chem. 2024 Apr 7;271:116398. doi: 10.1016/j.ejmech.2024.116398. Online ahead of print.ABSTRACTIn contemporary studies, the predominant utilization of C60 derivatives pertains to their role as photosensitizers or agents that scavenge free radicals. The intriguing coexistence of these divergent functionalities has prompted extensive investigation into water-soluble fullerenes. The photodynamic properties of these compounds find practical applications in DNA cleavage, antitumor interventions, and antibacterial endeavors. Consequently, photodynamic therapy is progressively emerging as a pivotal therapeutic modality w...
Source: European Journal of Medicinal Chemistry - April 13, 2024 Category: Chemistry Authors: Xue Bai Chungeng Dong Xinle Shao Faiz-Ur Rahman Huifang Hao Yongmin Zhang Source Type: research

Tetrazole derivatives in the management of neurological disorders: Recent advances on synthesis and pharmacological aspects
Eur J Med Chem. 2024 Apr 9;271:116388. doi: 10.1016/j.ejmech.2024.116388. Online ahead of print.ABSTRACTNeurological disorders are the leading cause of a large number of mortalities and morbidities. Nitrogen heterocyclic compounds have been pivotal in exhibiting wide array of therapeutic applications. Among them, tetrazole is a ubiquitous class of organic heterocyclic compounds that have attracted much attention because of its unique structural and chemical properties, and a wide range of pharmacological activities comprising anti-convulsant effect, antibiotic, anti-allergic, anti-hypertensive to name a few. Owing to signi...
Source: European Journal of Medicinal Chemistry - April 13, 2024 Category: Chemistry Authors: Shivangi Jaiswal Kanika Verma Jaya Dwivedi Swapnil Sharma Source Type: research

Opportunities and perspectives of small molecular phosphodiesterase inhibitors in neurodegenerative diseases
Eur J Med Chem. 2024 Apr 6;271:116386. doi: 10.1016/j.ejmech.2024.116386. Online ahead of print.ABSTRACTPhosphodiesterase (PDE) is a superfamily of enzymes that are responsible for the hydrolysis of two second messengers: cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). PDE inhibition promotes the gene transcription by activating cAMP-response element binding protein (CREB), initiating gene transcription of brain-derived neurotrophic factor (BDNF). The procedure exerts neuroprotective profile, and motor and cognitive improving efficacy. From this point of view, PDE inhibition will provide a ...
Source: European Journal of Medicinal Chemistry - April 13, 2024 Category: Chemistry Authors: Qi Li Qinghong Liao Shulei Qi He Huang Siyu He Weiping Lyu Jinxin Liang Huan Qin Zimeng Cheng Fan Yu Xue Dong Ziming Wang Lingfei Han Yantao Han Source Type: research