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.

Synergistic therapeutics: Co-targeting histone deacetylases and ribonucleotide reductase for enhanced cancer treatment
Eur J Med Chem. 2024 Mar 16;269:116324. doi: 10.1016/j.ejmech.2024.116324. Online ahead of print.ABSTRACTThe development of cancer is influenced by several variables, including altered protein expression, and signaling pathways. Cancers are inherently heterogeneous and exhibit genetic and epigenetic aberrations; therefore, developing therapies that act on numerous biological targets is encouraged. To achieve this, two approaches are employed: combination therapy and dual/multiple targeting chemotherapeutics. Two enzymes, histone deacetylases (HDACs) and ribonucleotide reductase (RR), are crucial for several biological func...
Source: European Journal of Medicinal Chemistry - March 23, 2024 Category: Chemistry Authors: Manasa Gangadhar Shetty Padmini Pai Mythili Padavu Kapaettu Satyamoorthy Babitha Kampa Sundara Source Type: research

Novel triterpenoid pyrones, phthalimides and phthalates are selectively cytotoxic in CCRF-CEM cancer cells - Synthesis, potency, and mitochondrial mechanism of action
Eur J Med Chem. 2024 Mar 18;269:116336. doi: 10.1016/j.ejmech.2024.116336. Online ahead of print.ABSTRACTA series of triterpenoid pyrones was synthesized and subsequently modified to introduce phthalimide or phthalate moieties into the triterpenoid skeleton. These compounds underwent in vitro cytotoxicity screening, revealing that a subset of six compounds exhibited potent activity, with IC50 values in the low micromolar range. Further biological evaluations, including Annexin V and propidium iodide staining experiment revealed, that all compounds induce selective apoptosis in cancer cells. Measurements of mitochondrial po...
Source: European Journal of Medicinal Chemistry - March 23, 2024 Category: Chemistry Authors: Anna Kazakova Ivo Frydrych Nikola Jakubcov á Jan Pokorn ý Barbora Li šková So ňa Gurská Petr D žubák Mari án Hajdúch Milan Urban Source Type: research

Recent research progress based on ferroptosis-related signaling pathways and the tumor microenvironment on it effects
Eur J Med Chem. 2024 Mar 7;269:116290. doi: 10.1016/j.ejmech.2024.116290. Online ahead of print.ABSTRACTThe existing therapies for cancer are not remote satisfactory due to drug-resistance in tumors that are malignant. There is a pressing necessity to take a step forward to develop innovative therapies that can complement current ones. Multiple investigations have demonstrated that ferroptosis therapy, a non-apoptotic modality of programmed cell death, has tremendous potential in face of multiple crucial events, such as drug resistance and toxicity in aggressive malignancies. Recently, ferroptosis at the crosswalk of chemo...
Source: European Journal of Medicinal Chemistry - March 22, 2024 Category: Chemistry Authors: Shijing Yu Lingwu Tong Jiangwen Shen Chenglei Li Yongshan Hu Keke Feng Jingwei Shao Source Type: research

Synthesis and biological evaluation of 1-phenyl-tetrahydro- β-carboline-based first dual PRMT5/EGFR inhibitors as potential anticancer agents
In this study, we designed and synthesized a series of 1-phenyl-tetrahydro-β-carboline (THβC) derivatives as the first class of dual PRMT5/EGFR inhibitors. Among the synthesized compounds, 10p showed the most potent dual PRMT5/EGFR inhibitory activity, with IC50 values of 15.47 ± 1.31 and 19.31 ± 2.14 μM, respectively. Compound 10p also exhibited promising antiproliferative activity against A549, MCF7, HeLa, and MDA-MB-231 cell lines, with IC50 values below 10 μM. Molecular docking studies suggested that 10p could bind to PRMT5 and EGFR through hydrophobic, π-π, and cation-π interactions. Furthermore, 10p displaye...
Source: European Journal of Medicinal Chemistry - March 22, 2024 Category: Chemistry Authors: Juan Zhang Xuliang Liu Na Sa Jin-He Zhang Yong-Si Cai Kai-Ming Wang Wei Xu Cheng-Shi Jiang Kong-Kai Zhu Source Type: research

Radioprotective effectiveness of a novel delta-tocotrienol prodrug on mouse hematopoietic system against < sup > 60 < /sup > Co gamma-ray irradiation through inducing granulocyte-colony stimulating factor production
In this study, we initially confirmed that DT3 exhibited the most significant potential for inducing G-CSF effects among eight natural vitamin E homologs. Consequently, we designed and synthesized a series of DT3 ester and ether derivatives, leading to improved radioprotective effects. The metabolic study conducted in vitro and in vivo has identified DT3 succinate 5b as a prodrug of DT3 with an approximately seven-fold higher bioavailability compared to DT3 alone. And DT3 ether derivative 8a were relatively stable and approximately 4 times more bioavailable than DT3 prototype. Furthermore, 5b exhibited superior ability to ...
Source: European Journal of Medicinal Chemistry - March 22, 2024 Category: Chemistry Authors: Zongchao Zuo Limei Wang Shaozheng Wang Xinyu Liu Dandan Wu Zhangyi Ouyang Ruoxi Meng Yajun Shan Shouguo Zhang Tao Peng Lin Wang Zhongtang Li Yuwen Cong Source Type: research

Discovery of novel polyheterocyclic neuraminidase inhibitors with 1,3,4-oxadiazole thioetheramide as core backbone
Eur J Med Chem. 2024 Mar 12;269:116305. doi: 10.1016/j.ejmech.2024.116305. Online ahead of print.ABSTRACTInspired by our earlier findings regarding neuraminidase (NA) inhibitors interacting with 150-cavity or 430-cavity of NA, sixteen novel polyheterocyclic NA inhibitors with 1,3,4-oxadiazole thioetheramide as core backbone were designed and synthesized based on the lead compound ZINC13401480. Of the synthesized compounds, compound N5 targeting 150-cavity exerts the best inhibitory activity against the wild-type H5N1 NA, with IC50 value of 0.14 μM, which is superior to oseltamivir carboxylate (OSC) (IC50 = 0.31 μM). Comp...
Source: European Journal of Medicinal Chemistry - March 22, 2024 Category: Chemistry Authors: Lin Lin Shang Zhi Jian Zhong Li Ping Cheng Source Type: research

Recent advances in the exploration of oxazolidinone scaffolds from compound development to antibacterial agents and other bioactivities
Eur J Med Chem. 2024 Mar 13;269:116326. doi: 10.1016/j.ejmech.2024.116326. Online ahead of print.ABSTRACTBacterial infections cause a variety of life-threatening diseases, and the continuous evolution of drug-resistant bacteria poses an increasing threat to current antimicrobial regimens. Gram-positive bacteria (GPB) have a wide range of genetic capabilities that allow them to adapt to and develop resistance to practically all existing antibiotics. Oxazolidinones, a class of potent bacterial protein synthesis inhibitors with a unique mechanism of action involving inhibition of bacterial ribosomal translation, has emerged a...
Source: European Journal of Medicinal Chemistry - March 21, 2024 Category: Chemistry Authors: Maxwell Ampomah-Wireko Shengcong Chen Ruirui Li Chen Gao Meng Wang Ye Qu Hongtao Kong Lauraine Nininahazwe En Zhang Source Type: research

Synthetic approaches and clinical application of small-molecule inhibitors of sodium-dependent glucose transporters 2 for the treatment of type 2 diabetes mellitus
Eur J Med Chem. 2024 Mar 18;269:116343. doi: 10.1016/j.ejmech.2024.116343. Online ahead of print.ABSTRACTSodium-dependent glucose transporters 2 (SGLT2) inhibitors are a class of small-molecule drugs that have gained significant attention in recent years for their potential clinical applications in the treatment of type 2 diabetes mellitus (T2DM). These inhibitors function by obstructing the kidneys' ability to reabsorb glucose, resulting in a rise in the excretion of glucose in urine (UGE) and subsequently lowering blood glucose levels. Several SGLT2 inhibitors, such as Dapagliflozin, Canagliflozin, and Empagliflozin, hav...
Source: European Journal of Medicinal Chemistry - March 21, 2024 Category: Chemistry Authors: Tong Xie Li-Jie Zhao Source Type: research

Cathepsin B: The dawn of tumor therapy
This article elucidates the relationship between CTSB and cancer from the perspectives of its structure, function, and role in tumor growth, migration, invasion, metastasis, angiogenesis and autophagy. Further, we summarized the research progress of cancer treatment related drugs targeting CTSB, as well as the potential and advantages of Traditional Chinese medicine in treating tumors by regulating the expression of CTSB.PMID:38508117 | DOI:10.1016/j.ejmech.2024.116329 (Source: European Journal of Medicinal Chemistry)
Source: European Journal of Medicinal Chemistry - March 20, 2024 Category: Chemistry Authors: Fuxian Liu Ting Zhou Shangzu Zhang Yangyang Li Yan Chen Zhiming Miao Xin Wang Gengqiang Yang Qiyang Li Liying Zhang Yongqi Liu Source Type: research

Synthesis and anti-liver fibrosis activity of imidazole and thiazole compounds containing amino acids
Eur J Med Chem. 2024 Mar 13;269:116311. doi: 10.1016/j.ejmech.2024.116311. Online ahead of print.ABSTRACTFour series of imidazoles (15a-g, 20c, and 20d) and thiazoles (18a-g, 22a, and 22b) possessing various amino acids were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. Among them, compounds 15g and 18c showed the highest inhibitory activity against ALK5, with IC50 values of 0.017 and 0.025 μM, respectively. Compounds 15g and 18c efficiently inhibited extracellular matrix (ECM) deposition in TGF-β-induced hepatic stellate cells (HSCs), and eventually supp...
Source: European Journal of Medicinal Chemistry - March 20, 2024 Category: Chemistry Authors: Yu-Qing Meng Jie Ren Jing-Xin Sun Fang-Yan Guo Jun-Zhe Min Ji-Xing Nan Ji-Shan Quan Li-Hua Lian Cheng-Hua Jin Source Type: research

Progress on synthesis and structure-activity relationships of lamellarins over the past decade
Eur J Med Chem. 2024 Mar 6;269:116294. doi: 10.1016/j.ejmech.2024.116294. Online ahead of print.ABSTRACTLamellarins are polyaromatic alkaloids isolated from marine organisms, including mollusks, tunicates, and sponges. Currently, over 60 structurally distinct natural lamellarins have been reported, and most of them exhibit promising biological activities, such as topoisomerase inhibition, mitochondrial function inhibition, multidrug resistance reversing, and anti-HIV activity. There has also been a significant progress on the synthetic study of lamellarins which has been regularly updated by numerous medicinal chemists as ...
Source: European Journal of Medicinal Chemistry - March 20, 2024 Category: Chemistry Authors: Mingze Wei Jing Chen Yuliang Song Jean-Philippe Monserrat Yongmin Zhang Li Shen Source Type: research

Evaluation of novel 2-(quinoline-2-ylthio)acetamide derivatives linked to diphenyl-imidazole as α-glucosidase inhibitors: Insights from in silico, in vitro, and in vivo studies on their anti-diabetic properties
In conclusion, novel 2-(quinoline-2-ylthio)acetamide derivatives as potent α-glucosidase inhibitors were developed. Compound 10c emerged as a promising candidate for diabetes management, warranting further investigation for potential clinical applications and mechanistic insights.PMID:38508120 | DOI:10.1016/j.ejmech.2024.116332 (Source: European Journal of Medicinal Chemistry)
Source: European Journal of Medicinal Chemistry - March 20, 2024 Category: Chemistry Authors: Minoo Khalili Ghomi Milad Noori Maryam Mirahmad Aida Iraji Ahmad Shahir Sadr Navid Dastyafteh Pooria Asili Mahdi Gholami Shahrzad Javanshir Maryam Lotfi Somayeh Mojtabavi Mohammad Ali Faramarzi Mehdi Asadi Ensieh Nasli-Esfahani Mahdie Palimi Bagher Larija Source Type: research