European Journal of Medicinal Chemistry 
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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.An update on antibacterial AlkylGuanidino Ureas: Design of new derivatives, synergism with colistin and data analysis of the whole library
Eur J Med Chem. 2024 Mar 28;270:116362. doi: 10.1016/j.ejmech.2024.116362. Online ahead of print.ABSTRACTAntimicrobial resistance (AMR) represents one of the most challenging global Public Health issues, with an alarmingly increasing rate of attributable mortality. This scenario highlights the urgent need for innovative medicinal strategies showing activity on resistant isolates (especially, carbapenem-resistant Gram-negative bacteria, methicillin-resistant S. aureus, and vancomycin-resistant enterococci) yielding new approaches for the treatment of bacterial infections. We previously reported AlkylGuanidino Ureas (AGUs) w...
Source: European Journal of Medicinal Chemistry - April 4, 2024 Category: Chemistry Authors: Claudia Ardino Filomena Sannio Giulio Poli Salvatore Galati Elena Dreassi Lorenzo Botta Jean-Denis Docquier Ilaria D'Agostino Source Type: research
Design, synthesis, and biological evaluation of first-in-class FABP1 inhibitors for the treatment of NASH
This study might be provided a promising insight into the field of NASH and inspiration for the development of FABP1 inhibitors.PMID:38574638 | DOI:10.1016/j.ejmech.2024.116358 (Source: European Journal of Medicinal Chemistry)
Source: European Journal of Medicinal Chemistry - April 4, 2024 Category: Chemistry Authors: Ya Chen Mingyang Yu Lianru Chen Jianming Mao Wenxin Wang Zhongcheng Yang Zhijun Cao Yuxia Liu Min Wei Luyong Zhang Zheng Li Source Type: research
A series of indole-derived γ-hydroxy propiolate esters as potent anti-inflammatory agents: Design, synthesis, in-vitro and in-vivo biological studies
Eur J Med Chem. 2024 Mar 30;270:116376. doi: 10.1016/j.ejmech.2024.116376. Online ahead of print.ABSTRACTA variety of novel indole-derived γ-hydroxy propiolate esters were designed, synthesized, and evaluated for their anti-inflammatory activity in-vitro and in-vivo. According to the nitric oxide (NO) inhibitory analysis, all compounds showed potent NO inhibitory ability in a dose-dependent manner, with no apparent cytotoxicity. The model compound, L-37, also exhibited significant potency in PGE2 inhibition. In addition, compounds L-37 and L-39 can downregulate the expression of COX-2 enzyme at 5 μM via ELISA experiment....
Source: European Journal of Medicinal Chemistry - April 3, 2024 Category: Chemistry Authors: Maryam Akhtar Luhao Lai Ting Tian Xu Zhang Hao Cheng Li Lin Source Type: research
Drug development and potential targets for Cushing's syndrome
Eur J Med Chem. 2024 Mar 22;270:116333. doi: 10.1016/j.ejmech.2024.116333. Online ahead of print.ABSTRACTCushing's syndrome (CS) is a complex disorder characterized by the excessive secretion of cortisol, with Cushing's disease (CD), particularly associated with pituitary tumors, exhibiting heightened morbidity and mortality. Although transsphenoidal pituitary surgery (TSS) stands as the primary treatment for CD, there is a crucial need to optimize patient prognosis. Current medical therapy serves as an adjunctive measure due to its unsatisfactory efficacy and unpredictable side effects. In this comprehensive review, we de...
Source: European Journal of Medicinal Chemistry - April 3, 2024 Category: Chemistry Authors: Wei Wei Qianqian Xu Liuyi Wu Guangyue Gong Yucheng Tian Huidan Huang Zhiyu Li Source Type: research
A series of indole-derived γ-hydroxy propiolate esters as potent anti-inflammatory agents: Design, synthesis, in-vitro and in-vivo biological studies
Eur J Med Chem. 2024 Mar 30;270:116376. doi: 10.1016/j.ejmech.2024.116376. Online ahead of print.ABSTRACTA variety of novel indole-derived γ-hydroxy propiolate esters were designed, synthesized, and evaluated for their anti-inflammatory activity in-vitro and in-vivo. According to the nitric oxide (NO) inhibitory analysis, all compounds showed potent NO inhibitory ability in a dose-dependent manner, with no apparent cytotoxicity. The model compound, L-37, also exhibited significant potency in PGE2 inhibition. In addition, compounds L-37 and L-39 can downregulate the expression of COX-2 enzyme at 5 μM via ELISA experiment....
Source: European Journal of Medicinal Chemistry - April 3, 2024 Category: Chemistry Authors: Maryam Akhtar Luhao Lai Ting Tian Xu Zhang Hao Cheng Li Lin Source Type: research
Drug development and potential targets for Cushing's syndrome
Eur J Med Chem. 2024 Mar 22;270:116333. doi: 10.1016/j.ejmech.2024.116333. Online ahead of print.ABSTRACTCushing's syndrome (CS) is a complex disorder characterized by the excessive secretion of cortisol, with Cushing's disease (CD), particularly associated with pituitary tumors, exhibiting heightened morbidity and mortality. Although transsphenoidal pituitary surgery (TSS) stands as the primary treatment for CD, there is a crucial need to optimize patient prognosis. Current medical therapy serves as an adjunctive measure due to its unsatisfactory efficacy and unpredictable side effects. In this comprehensive review, we de...
Source: European Journal of Medicinal Chemistry - April 3, 2024 Category: Chemistry Authors: Wei Wei Qianqian Xu Liuyi Wu Guangyue Gong Yucheng Tian Huidan Huang Zhiyu Li Source Type: research
Targeting EGFR degradation by autophagosome degraders
Eur J Med Chem. 2024 Mar 26;270:116345. doi: 10.1016/j.ejmech.2024.116345. Online ahead of print.ABSTRACTSeveral generations of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have been developed for the treatment of non-small cell lung cancer (NSCLC) in clinic. However, emerging drug resistance mediated by new EGFR mutations or activations by pass, leads to malignant progression of NSCLC. Proteolysis targeting chimeras (PROTACs) have been utilized to overcome the drug resistance acquired by mutant EGFR, newly potent and selective degraders are still need to be developed for clinical applications. Herein...
Source: European Journal of Medicinal Chemistry - April 2, 2024 Category: Chemistry Authors: ZhongFeng Zhu Jiaying Li Shujun Shen Hawaa Al-Furas Shengrong Li Yichen Tong Yi Li Yucheng Zeng Qianyi Feng Kaiyue Chen Nan Ma Fengtao Zhou Zhang Zhang Zhengqiu Li Jiyan Pang Ke Ding Fang Xu Source Type: research
Targeting EGFR degradation by autophagosome degraders
Eur J Med Chem. 2024 Mar 26;270:116345. doi: 10.1016/j.ejmech.2024.116345. Online ahead of print.ABSTRACTSeveral generations of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have been developed for the treatment of non-small cell lung cancer (NSCLC) in clinic. However, emerging drug resistance mediated by new EGFR mutations or activations by pass, leads to malignant progression of NSCLC. Proteolysis targeting chimeras (PROTACs) have been utilized to overcome the drug resistance acquired by mutant EGFR, newly potent and selective degraders are still need to be developed for clinical applications. Herein...
Source: European Journal of Medicinal Chemistry - April 2, 2024 Category: Chemistry Authors: ZhongFeng Zhu Jiaying Li Shujun Shen Hawaa Al-Furas Shengrong Li Yichen Tong Yi Li Yucheng Zeng Qianyi Feng Kaiyue Chen Nan Ma Fengtao Zhou Zhang Zhang Zhengqiu Li Jiyan Pang Ke Ding Fang Xu Source Type: research
Discovery of a novel homoisoflavonoid derivative 5g for anti-osteoclastic bone loss via targeting FGFR1
In this study, we prepared a series of novel homoisoflavonoid (HIF) derivatives to evaluate their inhibitory effects on osteoclastogenesis using TRAP-activity in vitro assay. Then, the preliminary structure-activity relationship was studied. Among the evaluated novel flavonoids, derivative 5g exerted the most inhibitory bioactivity on primary osteoclast differentiation without interfering with osteogenesis. It was hence selected for further in vitro, in vivo and mechanism of action investigation. Results show that 5g likely directly binds to the fibroblast growth factor receptor 1 (FGFR1), decreasing the activation of ERK1...
Source: European Journal of Medicinal Chemistry - March 31, 2024 Category: Chemistry Authors: Zhihao Chen Alessandra Marie Encarnacion Robin Prakash Sirvin Rajan Hongyuan Yao Sunwoo Lee Eunae Kim Tae-Hoon Lee Source Type: research
Natural products as non-covalent and covalent modulators of the KEAP1/NRF2 pathway exerting antioxidant effects
Eur J Med Chem. 2024 Mar 26;270:116355. doi: 10.1016/j.ejmech.2024.116355. Online ahead of print.ABSTRACTBy controlling several antioxidant and detoxifying genes at the transcriptional level, including NAD(P)H quinone oxidoreductase 1 (NQO1), multidrug resistance-associated proteins (MRPs), UDP-glucuronosyltransferase (UGT), glutamate-cysteine ligase catalytic (GCLC) and modifier (GCLM) subunits, glutathione S-transferase (GST), sulfiredoxin1 (SRXN1), and heme-oxygenase-1 (HMOX1), the KEAP1/NRF2 pathway plays a crucial role in the oxidative stress response. Accordingly, the discovery of modulators of this pathway, activati...
Source: European Journal of Medicinal Chemistry - March 31, 2024 Category: Chemistry Authors: Giulia Culletta Brigitta Buttari Marzia Arese Simone Brogi Anna Maria Almerico Luciano Saso Marco Tutone Source Type: research
Insights into the development of < sup > 99m < /sup > Tc-radioligands for serotonergic receptors imaging: Synthesis, labeling, In vitro, and In vivo studies
Eur J Med Chem. 2024 Mar 23;270:116349. doi: 10.1016/j.ejmech.2024.116349. Online ahead of print.ABSTRACTSerotonergic (5-hydroxytryptamine; 5-HT) receptors play critical roles in neurological and psychological disorders such as schizophrenia, anxiety, depression, and Alzheimer's diseases. Therefore, it is particularly important to develop novel radioligands or modify the existing ones to identify the serotonergic receptors involved in psychiatric disorders. Among the 16 subtypes of serotonergic systems, only technetium-99m based radiopharmaceuticals have been evaluated for serotonin-1A (5-HT1A), serotonin-2A (5-HT2A), 5-HT...
Source: European Journal of Medicinal Chemistry - March 31, 2024 Category: Chemistry Authors: Shahnaz Saednia Saeed Emami Masoud Moslehi Seyed Jalal Hosseinimehr Source Type: research
Discovery of a novel homoisoflavonoid derivative 5g for anti-osteoclastic bone loss via targeting FGFR1
In this study, we prepared a series of novel homoisoflavonoid (HIF) derivatives to evaluate their inhibitory effects on osteoclastogenesis using TRAP-activity in vitro assay. Then, the preliminary structure-activity relationship was studied. Among the evaluated novel flavonoids, derivative 5g exerted the most inhibitory bioactivity on primary osteoclast differentiation without interfering with osteogenesis. It was hence selected for further in vitro, in vivo and mechanism of action investigation. Results show that 5g likely directly binds to the fibroblast growth factor receptor 1 (FGFR1), decreasing the activation of ERK1...
Source: European Journal of Medicinal Chemistry - March 31, 2024 Category: Chemistry Authors: Zhihao Chen Alessandra Marie Encarnacion Robin Prakash Sirvin Rajan Hongyuan Yao Sunwoo Lee Eunae Kim Tae-Hoon Lee Source Type: research
Natural products as non-covalent and covalent modulators of the KEAP1/NRF2 pathway exerting antioxidant effects
Eur J Med Chem. 2024 Mar 26;270:116355. doi: 10.1016/j.ejmech.2024.116355. Online ahead of print.ABSTRACTBy controlling several antioxidant and detoxifying genes at the transcriptional level, including NAD(P)H quinone oxidoreductase 1 (NQO1), multidrug resistance-associated proteins (MRPs), UDP-glucuronosyltransferase (UGT), glutamate-cysteine ligase catalytic (GCLC) and modifier (GCLM) subunits, glutathione S-transferase (GST), sulfiredoxin1 (SRXN1), and heme-oxygenase-1 (HMOX1), the KEAP1/NRF2 pathway plays a crucial role in the oxidative stress response. Accordingly, the discovery of modulators of this pathway, activati...
Source: European Journal of Medicinal Chemistry - March 31, 2024 Category: Chemistry Authors: Giulia Culletta Brigitta Buttari Marzia Arese Simone Brogi Anna Maria Almerico Luciano Saso Marco Tutone Source Type: research
Insights into the development of < sup > 99m < /sup > Tc-radioligands for serotonergic receptors imaging: Synthesis, labeling, In vitro, and In vivo studies
Eur J Med Chem. 2024 Mar 23;270:116349. doi: 10.1016/j.ejmech.2024.116349. Online ahead of print.ABSTRACTSerotonergic (5-hydroxytryptamine; 5-HT) receptors play critical roles in neurological and psychological disorders such as schizophrenia, anxiety, depression, and Alzheimer's diseases. Therefore, it is particularly important to develop novel radioligands or modify the existing ones to identify the serotonergic receptors involved in psychiatric disorders. Among the 16 subtypes of serotonergic systems, only technetium-99m based radiopharmaceuticals have been evaluated for serotonin-1A (5-HT1A), serotonin-2A (5-HT2A), 5-HT...
Source: European Journal of Medicinal Chemistry - March 31, 2024 Category: Chemistry Authors: Shahnaz Saednia Saeed Emami Masoud Moslehi Seyed Jalal Hosseinimehr Source Type: research
Activity refinement of aryl amino acetamides that target the P. falciparum STAR-related lipid transfer 1 protein
In this study, we combined structural elements from the different aryl acetamide hit subtypes and explored the structure-activity relationship. It was shown that the inclusion of an endocyclic nitrogen, to generate the tool compound WJM-715, improved aqueous solubility and modestly improved metabolic stability in rat hepatocytes. Metabolic stability in human liver microsomes remains a challenge for future development of the aryl acetamide class, which was underscored by modest systemic exposure and a short half-life in mice. The optimized aryl acetamide analogs were cross resistant to parasites with mutations in PfSTART1, ...
Source: European Journal of Medicinal Chemistry - March 30, 2024 Category: Chemistry Authors: William Nguyen Coralie Boulet Madeline G Dans Katie Loi Kate E Jarman Gabrielle M Watson Wai-Hong Tham Kate J Fairhurst Tomas Yeo David A Fidock Sergio Wittlin Mrittika Chowdury Tania F de Koning-Ward Gong Chen Dandan Yan Susan A Charman Delphine Baud Ste Source Type: research
