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.

Identification of dihydroquinolizinone derivatives with nitrogen heterocycle moieties as new anti-HBV agents
In this study, we designed and synthesized a series of DHQs incorporating nitrogen heterocycle moieties. Almost all of these compounds exhibited potent inhibition activity against HBsAg, with IC50 values at the nanomolar level. Impressively, the compound (S)-2a (10 μM) demonstrated a comparatively reduced impact on the neurite outgrowth of HT22 cells and isolated mouse DRG neurons in comparison to RG7834, thereby indicating a decrease in neurotoxicity. Furthermore, (S)-2a exhibited higher drug exposures than RG7834. The potent anti-HBV activity, reduced neurotoxicity, and favorable pharmacokinetic profiles underscore its ...
Source: European Journal of Medicinal Chemistry - March 8, 2024 Category: Chemistry Authors: Huijuan Song Shangze Yang Shuo Wu Xiaoyu Qin Ya Wang Xican Ma Jiaqi Gong Meng Wei Apeng Wang Mengyuan Wang Kun Lan Juan Guo Mingliang Liu Xingjuan Chen Yuhuan Li Kai Lv Source Type: research

The discovery of potent USP2/USP8 dual-target inhibitors for the treatment of breast cancer via structure guided optimization of ML364
In this study, we developed a series of ML364 derivatives using ligand-based drug design strategies. The standout compound, LLK203, demonstrated enhanced inhibitory activity, showing a 4-fold increase against USP2 and a 9-fold increase against USP8, compared to the parent molecule. In MCF-7 breast cancer cells, LLK203 effectively degraded key proteins involved in cancer progression and notably inhibited cell proliferation. Moreover, LLK203 exhibited potent in vivo efficacy in the 4T1 homograft model, while maintaining a low toxicity profile. These results underscore the potential of LLK203 as a promising dual-target inhibi...
Source: European Journal of Medicinal Chemistry - March 7, 2024 Category: Chemistry Authors: Yucheng Tian Kang Liu Dongdong Wu Liuyi Wu Qianqian Xu Wei Wei Zhiyu Li Qianming Du Jinlei Bian Source Type: research

Structure modification of anoplin for fighting resistant bacteria
Eur J Med Chem. 2024 Feb 24;268:116276. doi: 10.1016/j.ejmech.2024.116276. Online ahead of print.ABSTRACTThe emergence of bacterial resistance has posed a significant challenge to clinical antimicrobial treatment, rendering commonly used antibiotics ineffective. The development of novel antimicrobial agents and strategies is imperative for the treatment of resistant bacterial infections. Antimicrobial peptides (AMPs) are considered a promising class of antimicrobial agents due to their low propensity for resistance and broad-spectrum activity. Anoplin is a small linear α-helical natural antimicrobial peptide that was isol...
Source: European Journal of Medicinal Chemistry - March 7, 2024 Category: Chemistry Authors: Chao Zhong Jing Zou Wenbo Mao Ping Yang Jingying Zhang Sanhu Gou Yun Zhang Hui Liu Jingman Ni Source Type: research

Design and biological evaluation of dual tubulin/HDAC inhibitors based on millepachine for treatment of prostate cancer
Eur J Med Chem. 2024 Mar 3;268:116301. doi: 10.1016/j.ejmech.2024.116301. Online ahead of print.ABSTRACTIn this work, a novel of dual tubulin/HDAC inhibitors were designed and synthesized based on the structure of natural product millepachine, which has been identified as a tubulin polymerization inhibitor. Biological evaluation revealed that compound 9n exhibited an impressive potency against PC-3 cells with the IC50 value of 16 nM and effectively inhibited both microtubule polymerization and HDAC activity. Furthermore, compound 9n not only induced cell cycle arrest at G2/M phase, but also induced PC- 3 cells apoptosis. F...
Source: European Journal of Medicinal Chemistry - March 7, 2024 Category: Chemistry Authors: Shanshan Xie Jiafu Leng Shifang Zhao Liqiao Zhu Mengyu Zhang Mengdan Ning Bo Zhao Lingyi Kong Yong Yin Source Type: research

Research progress of DDR1 inhibitors in the treatment of multiple human diseases
Eur J Med Chem. 2024 Feb 27;268:116291. doi: 10.1016/j.ejmech.2024.116291. Online ahead of print.ABSTRACTDiscoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase (RTK) and plays pivotal roles in regulating cellular functions such as proliferation, differentiation, invasion, migration, and matrix remodeling. DDR1 is involved in the occurrence and progression of many human diseases, including cancer, fibrosis, and inflammation. Therefore, DDR1 represents a highly promising therapeutic target. Although no selective small-molecule inhibitors have reached clinical trials to date, many molecules have s...
Source: European Journal of Medicinal Chemistry - March 7, 2024 Category: Chemistry Authors: Mengying Liu Jifa Zhang Xiaoxue Li Yuxi Wang Source Type: research

Advances in molecular agents targeting toll-like receptor 4 signaling pathways for potential treatment of sepsis
Eur J Med Chem. 2024 Mar 2;268:116300. doi: 10.1016/j.ejmech.2024.116300. Online ahead of print.ABSTRACTSepsis is a systemic inflammatory response syndrome caused by an infection. Toll-like receptor 4 (TLR4) is activated by endogenous molecules released by injured or necrotic tissues. Additionally, TLR4 is remarkably sensitive to infection of various bacteria and can rapidly stimulate host defense responses. The TLR4 signaling pathway plays an important role in sepsis by activating the inflammatory response. Accordingly, as part of efforts to improve the inflammatory response and survival rate of patients with sepsis, seve...
Source: European Journal of Medicinal Chemistry - March 7, 2024 Category: Chemistry Authors: Yunyun Zheng Yingying Gao Weiru Zhu Xian-Guang Bai Jinxu Qi Source Type: research

Optimizing drug-like properties of selective butyrylcholinesterase inhibitors for cognitive improvement: Enhancing aqueous solubility by disrupting molecular plane
In this study, the previously obtained selective BChE inhibitors with benzimidazole-oxadiazole scaffold were further structurally modified to increase their aqueous solubility and pharmacokinetic (PK) characteristics. S16-1029 showed improved solubility (3280 μM, upgraded by 14 times) and PK parameters, including plasma exposure (AUC0-inf = 1729.95 ng/mL*h, upgraded by 2.6 times) and oral bioavailability (Fpo = 48.18%, upgraded by 2 times). S16-1029 also displayed weak or no inhibition against Cytochrome P450 (CYP450) and human ether a-go-go related gene (hERG) potassium channel. In vivo experiments on tissue distribution...
Source: European Journal of Medicinal Chemistry - March 7, 2024 Category: Chemistry Authors: Shuaishuai Xing Xu Tang Leyan Wang Jun Wang Bingbing Lv Xiaolong Wang Can Guo Ye Zhao Feng Feng Wenyuan Liu Yao Chen Haopeng Sun Source Type: research

The discovery of potent USP2/USP8 dual-target inhibitors for the treatment of breast cancer via structure guided optimization of ML364
In this study, we developed a series of ML364 derivatives using ligand-based drug design strategies. The standout compound, LLK203, demonstrated enhanced inhibitory activity, showing a 4-fold increase against USP2 and a 9-fold increase against USP8, compared to the parent molecule. In MCF-7 breast cancer cells, LLK203 effectively degraded key proteins involved in cancer progression and notably inhibited cell proliferation. Moreover, LLK203 exhibited potent in vivo efficacy in the 4T1 homograft model, while maintaining a low toxicity profile. These results underscore the potential of LLK203 as a promising dual-target inhibi...
Source: European Journal of Medicinal Chemistry - March 7, 2024 Category: Chemistry Authors: Yucheng Tian Kang Liu Dongdong Wu Liuyi Wu Qianqian Xu Wei Wei Zhiyu Li Qianming Du Jinlei Bian Source Type: research

Structure modification of anoplin for fighting resistant bacteria
Eur J Med Chem. 2024 Feb 24;268:116276. doi: 10.1016/j.ejmech.2024.116276. Online ahead of print.ABSTRACTThe emergence of bacterial resistance has posed a significant challenge to clinical antimicrobial treatment, rendering commonly used antibiotics ineffective. The development of novel antimicrobial agents and strategies is imperative for the treatment of resistant bacterial infections. Antimicrobial peptides (AMPs) are considered a promising class of antimicrobial agents due to their low propensity for resistance and broad-spectrum activity. Anoplin is a small linear α-helical natural antimicrobial peptide that was isol...
Source: European Journal of Medicinal Chemistry - March 7, 2024 Category: Chemistry Authors: Chao Zhong Jing Zou Wenbo Mao Ping Yang Jingying Zhang Sanhu Gou Yun Zhang Hui Liu Jingman Ni Source Type: research

Design and biological evaluation of dual tubulin/HDAC inhibitors based on millepachine for treatment of prostate cancer
Eur J Med Chem. 2024 Mar 3;268:116301. doi: 10.1016/j.ejmech.2024.116301. Online ahead of print.ABSTRACTIn this work, a novel of dual tubulin/HDAC inhibitors were designed and synthesized based on the structure of natural product millepachine, which has been identified as a tubulin polymerization inhibitor. Biological evaluation revealed that compound 9n exhibited an impressive potency against PC-3 cells with the IC50 value of 16 nM and effectively inhibited both microtubule polymerization and HDAC activity. Furthermore, compound 9n not only induced cell cycle arrest at G2/M phase, but also induced PC- 3 cells apoptosis. F...
Source: European Journal of Medicinal Chemistry - March 7, 2024 Category: Chemistry Authors: Shanshan Xie Jiafu Leng Shifang Zhao Liqiao Zhu Mengyu Zhang Mengdan Ning Bo Zhao Lingyi Kong Yong Yin Source Type: research

Research progress of DDR1 inhibitors in the treatment of multiple human diseases
Eur J Med Chem. 2024 Feb 27;268:116291. doi: 10.1016/j.ejmech.2024.116291. Online ahead of print.ABSTRACTDiscoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase (RTK) and plays pivotal roles in regulating cellular functions such as proliferation, differentiation, invasion, migration, and matrix remodeling. DDR1 is involved in the occurrence and progression of many human diseases, including cancer, fibrosis, and inflammation. Therefore, DDR1 represents a highly promising therapeutic target. Although no selective small-molecule inhibitors have reached clinical trials to date, many molecules have s...
Source: European Journal of Medicinal Chemistry - March 7, 2024 Category: Chemistry Authors: Mengying Liu Jifa Zhang Xiaoxue Li Yuxi Wang Source Type: research

Advances in molecular agents targeting toll-like receptor 4 signaling pathways for potential treatment of sepsis
Eur J Med Chem. 2024 Mar 2;268:116300. doi: 10.1016/j.ejmech.2024.116300. Online ahead of print.ABSTRACTSepsis is a systemic inflammatory response syndrome caused by an infection. Toll-like receptor 4 (TLR4) is activated by endogenous molecules released by injured or necrotic tissues. Additionally, TLR4 is remarkably sensitive to infection of various bacteria and can rapidly stimulate host defense responses. The TLR4 signaling pathway plays an important role in sepsis by activating the inflammatory response. Accordingly, as part of efforts to improve the inflammatory response and survival rate of patients with sepsis, seve...
Source: European Journal of Medicinal Chemistry - March 7, 2024 Category: Chemistry Authors: Yunyun Zheng Yingying Gao Weiru Zhu Xian-Guang Bai Jinxu Qi Source Type: research

Optimizing drug-like properties of selective butyrylcholinesterase inhibitors for cognitive improvement: Enhancing aqueous solubility by disrupting molecular plane
In this study, the previously obtained selective BChE inhibitors with benzimidazole-oxadiazole scaffold were further structurally modified to increase their aqueous solubility and pharmacokinetic (PK) characteristics. S16-1029 showed improved solubility (3280 μM, upgraded by 14 times) and PK parameters, including plasma exposure (AUC0-inf = 1729.95 ng/mL*h, upgraded by 2.6 times) and oral bioavailability (Fpo = 48.18%, upgraded by 2 times). S16-1029 also displayed weak or no inhibition against Cytochrome P450 (CYP450) and human ether a-go-go related gene (hERG) potassium channel. In vivo experiments on tissue distribution...
Source: European Journal of Medicinal Chemistry - March 7, 2024 Category: Chemistry Authors: Shuaishuai Xing Xu Tang Leyan Wang Jun Wang Bingbing Lv Xiaolong Wang Can Guo Ye Zhao Feng Feng Wenyuan Liu Yao Chen Haopeng Sun Source Type: research

Design, synthesis and antibacterial evaluation of low toxicity amphiphilic-cephalosporin derivatives
In this study, two series of amphiphilic-cephalosporins were designed and synthesized, several of which showed good antibacterial activity against both Gram-positive and Gram-negative bacteria. Structure-activity relationships indicated that the length of the hydrophobic alkyl chain significantly affects the antibacterial activity against Gram-negative bacteria. The best compound 2d showed high activity against drug-susceptible Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) with MICs of 0.5 and 2-4 μg/mL, respectively. Furthermore, 2d remained active in complex mammalian body fluids and had a...
Source: European Journal of Medicinal Chemistry - March 6, 2024 Category: Chemistry Authors: Shengcong Chen Shangshang Qin Ruirui Li Ye Qu Maxwell Ampomah-Wireko Lauraine Nininahazwe Meng Wang Chen Gao En Zhang Source Type: research

Design, synthesis and antibacterial evaluation of low toxicity amphiphilic-cephalosporin derivatives
In this study, two series of amphiphilic-cephalosporins were designed and synthesized, several of which showed good antibacterial activity against both Gram-positive and Gram-negative bacteria. Structure-activity relationships indicated that the length of the hydrophobic alkyl chain significantly affects the antibacterial activity against Gram-negative bacteria. The best compound 2d showed high activity against drug-susceptible Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) with MICs of 0.5 and 2-4 μg/mL, respectively. Furthermore, 2d remained active in complex mammalian body fluids and had a...
Source: European Journal of Medicinal Chemistry - March 6, 2024 Category: Chemistry Authors: Shengcong Chen Shangshang Qin Ruirui Li Ye Qu Maxwell Ampomah-Wireko Lauraine Nininahazwe Meng Wang Chen Gao En Zhang Source Type: research