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.

Novel sulfonamide-indolinone hybrids targeting mitochondrial respiration of breast cancer cells
Eur J Med Chem. 2024 Feb 17;268:116255. doi: 10.1016/j.ejmech.2024.116255. Online ahead of print.ABSTRACTBreast cancer (BC) still poses a threat worldwide which demands continuous efforts to present safer and efficacious treatment options via targeted therapy. Beside kinases' aberrations as Aurora B kinase which controls cell division, BC adopts distinct metabolic profiles to meet its high energy demands. Accordingly, targeting both aurora B kinase and/or metabolic vulnerability presents a promising approach to tackle BC. Based on a previously reported indolinone-based Aurora B kinase inhibitor (III), and guided by structu...
Source: European Journal of Medicinal Chemistry - February 24, 2024 Category: Chemistry Authors: Sama W A Helmy Amal Kamal Abdel-Aziz Eman M E Dokla Tarek E Ahmed Yasmin Hatem Engy A Abdel Rahman Marwa Sharaky Mai I Shahin Eman Z Elrazaz Rabah A T Serya Maged Henary Sameh S Ali Dalal A Abou El Ella Source Type: research

Design, synthesis, and biological evaluation of first-in-class indomethacin-based PROTACs degrading SARS-CoV-2 main protease and with broad-spectrum antiviral activity
Eur J Med Chem. 2024 Feb 6;268:116202. doi: 10.1016/j.ejmech.2024.116202. Online ahead of print.ABSTRACTTo date, Proteolysis Targeting Chimera (PROTAC) technology has been successfully applied to mediate proteasomal-induced degradation of several pharmaceutical targets mainly related to oncology, immune disorders, and neurodegenerative diseases. On the other hand, its exploitation in the field of antiviral drug discovery is still in its infancy. Recently, we described two indomethacin (INM)-based PROTACs displaying broad-spectrum antiviral activity against coronaviruses. Here, we report the design, synthesis, and character...
Source: European Journal of Medicinal Chemistry - February 23, 2024 Category: Chemistry Authors: Jenny Desantis Alessandro Bazzacco Michela Eleuteri Sara Tuci Elisa Bianconi Antonio Macchiarulo Beatrice Mercorelli Arianna Loregian Laura Goracci Source Type: research

Novel aroyl guanidine anti-trypanosomal compounds that exert opposing effects on parasite energy metabolism
Eur J Med Chem. 2024 Jan 17;268:116162. doi: 10.1016/j.ejmech.2024.116162. Online ahead of print.ABSTRACTHuman African trypanosomiasis (HAT), or sleeping sickness, is a neglected tropical disease with current treatments marred by severe side effects or delivery issues. To identify novel classes of compounds for the treatment of HAT, high throughput screening (HTS) had previously been conducted on bloodstream forms of T. b. brucei, a model organism closely related to the human pathogens T. b. gambiense and T. b. rhodesiense. This HTS had identified a number of structural classes with potent bioactivity against T. b. brucei ...
Source: European Journal of Medicinal Chemistry - February 23, 2024 Category: Chemistry Authors: Swapna Varghese Anubhav Srivastava Siu Wai Wong Thuy Le Noel Pitcher Mathilda Mesnard Camille Lallemand Raphael Rahmani Sarah R Moawad Fei Huang Tiantong He Brad E Sleebs Michael P Barrett Melissa L Sykes Vicky M Avery Darren J Creek Jonathan B Baell Source Type: research

What influences the activity of Degrader-Antibody conjugates (DACs)
Eur J Med Chem. 2024 Feb 3;268:116216. doi: 10.1016/j.ejmech.2024.116216. Online ahead of print.ABSTRACTThe targeted protein degradation (TPD) technology employing proteolysis-targeting chimeras (PROTACs) has been widely applied in drug chemistry and chemical biology for the treatment of cancer and other diseases. PROTACs have demonstrated significant advantages in targeting undruggable targets and overcoming drug resistance. However, despite the efficient degradation of targeted proteins achieved by PROTACs, they still face challenges related to selectivity between normal and cancer cells, as well as issues with poor memb...
Source: European Journal of Medicinal Chemistry - February 22, 2024 Category: Chemistry Authors: Yaolin Guo Xiaoxue Li Yang Xie Yuxi Wang Source Type: research

Inhibition of the thioredoxin system for radiosensitization therapy of cancer
Eur J Med Chem. 2024 Feb 9;268:116218. doi: 10.1016/j.ejmech.2024.116218. Online ahead of print.ABSTRACTRadiotherapy (RT) stands as a cornerstone in the clinical armamentarium against various cancers due to its proven efficacy. However, the intrinsic radiation resistance exhibited by cancer cells, coupled with the adverse effects of RT on normal tissues, often compromises its therapeutic potential and leads to unwanted side effects. This comprehensive review aims to consolidate our understanding of how radiosensitizers inhibit the thioredoxin (Trx) system in cellular contexts. Notable radiosensitizers, including gold nanop...
Source: European Journal of Medicinal Chemistry - February 22, 2024 Category: Chemistry Authors: Yisheng Cao Xiedong Zhou Qiuying Nie Junmin Zhang Source Type: research

Rare flavanone-diarylheptanoid hybrids from Typha angustifolia shows anti breast cancer activity via activating TGF- β1/Smad signaling pathway
Eur J Med Chem. 2024 Feb 15;268:116220. doi: 10.1016/j.ejmech.2024.116220. Online ahead of print.ABSTRACTFour new flavanone-diarylheptanoid hetero dimers, typhatifolins A-D (1-4), were separated from the pollen of a widely distributed medicinal plant Typha angustifolia. Structures of these rare hybrids were elucidated by detailed interpretation of spectroscopic data, and their absolute configurations were determined on the basis of Mosher's method and ECD analyses. All the four compounds showed moderate to significant cytotoxicities against a panel of tumor cell lines with IC50 values ranging from 0.67 to 12.48 μM. Furthe...
Source: European Journal of Medicinal Chemistry - February 22, 2024 Category: Chemistry Authors: Yu-Peng Li Hu Liu Xue-Chun Zhao Xue-Lian Tang Peipei Shan Hua Zhang Source Type: research

Thiadiazole-, selenadiazole- and triazole-fused anthraquinones as G-quadruplex targeting anticancer compounds
In this study we proposed an original scheme for synthesis of azole-fused anthraquinones and prepared a series of G4 ligands carrying amino- or guanidinoalkylamino side chains. The heterocyclic core and structure of the terminal groups strongly affect on binding to G4-forming oligonucleotides, cellular accumulation and antitumor potency of compounds. In particular, thiadiazole- and selenadiazole- but not triazole-based ligands inhibit the proliferation of tumor cells (e.g. K562 leukemia) and stabilize primarily telomeric and c-MYC G4s. Anthraselenadiazole derivative 11a showed a good affinity to c-MYC G4 in vitro and down-...
Source: European Journal of Medicinal Chemistry - February 22, 2024 Category: Chemistry Authors: Daria V Andreeva Tatiana S Vedekhina Alexander S Gostev Lyubov G Dezhenkova Yulia L Volodina Alina A Markova Minh Tuan Nguyen Olga M Ivanova Vladislava А Dolgusheva Anna M Varizhuk Alexander S Tikhomirov Andrey E Shchekotikhin Source Type: research

Deep learning for advancing peptide drug development: Tools and methods in structure prediction and design
Eur J Med Chem. 2024 Feb 19;268:116262. doi: 10.1016/j.ejmech.2024.116262. Online ahead of print.ABSTRACTPeptides can bind challenging disease targets with high affinity and specificity, offering enormous opportunities for addressing unmet medical needs. However, peptides' unique features, including smaller size, increased structural flexibility, and limited data availability, pose additional challenges to the design process compared to proteins. This review explores the dynamic field of peptide therapeutics, leveraging deep learning to enhance structure prediction and design. Our exploration encompasses various facets of ...
Source: European Journal of Medicinal Chemistry - February 22, 2024 Category: Chemistry Authors: Xinyi Wu Huitian Lin Renren Bai Hongliang Duan Source Type: research

Identification of 3-aryl-5-methyl-isoxazole-4-carboxamide derivatives and analogs as novel HIF-2 α agonists through docking-based virtual screening and structural modification
Eur J Med Chem. 2024 Feb 16;268:116227. doi: 10.1016/j.ejmech.2024.116227. Online ahead of print.ABSTRACTHypoxia-inducible factor-2 (HIF-2) serves as the pivotal transcription factor in cellular responses to low oxygen levels, particularly concerning the regulation of erythropoietin (EPO) production. A docking-based virtual screening on crystal structures of HIF-2α inhibitors unexpectedly identified 3-phenyl-5-methyl-isoxazole-4-carboxamide derivative v19 as a hit of HIF-2α agonist. Further structural optimizations of compound v19 led to the discovery of a series of HIF-2α agonists with novel scaffolds. The most promisi...
Source: European Journal of Medicinal Chemistry - February 22, 2024 Category: Chemistry Authors: Siyuan Chen Yao Liu Zhe Wang Chengcheng Qi Yanzhen Yu Lei Xu Tingjun Hou Rong Sheng Source Type: research

The BTLA-HVEM complex - The future of cancer immunotherapy
Eur J Med Chem. 2024 Feb 11;268:116231. doi: 10.1016/j.ejmech.2024.116231. Online ahead of print.ABSTRACTThe BTLA-HVEM complex plays a pivotal role in cancer and cancer immunotherapy by regulating immune responses. Dysregulation of BTLA and HVEM expression contributes to immunosuppression and tumor progression across various cancer types. Targeting the interaction between BTLA and HVEM holds promise for enhancing anti-tumor immune responses. Disruption of this complex presents a valuable avenue for advancing cancer immunotherapy strategies. Aberrant expression of BTLA and HVEM adversely affects immune cell function, partic...
Source: European Journal of Medicinal Chemistry - February 22, 2024 Category: Chemistry Authors: Karolina Wojciechowicz Marta Spodzieja Anna Wardowska Source Type: research

Discovery of FLT3-targeting PROTACs with potent antiproliferative activity against acute myeloid leukemia cells harboring FLT3 mutations
Eur J Med Chem. 2024 Feb 14;268:116237. doi: 10.1016/j.ejmech.2024.116237. Online ahead of print.ABSTRACTAcute myeloid leukemia (AML) patients harboring Fms-like tyrosine kinase 3 (FLT3) mutations often suffer from poor prognosis and relapse. Targeted protein degradation utilizing proteolysis targeting chimeras (PROTACs) is considered as a novel therapeutic strategy in drug discovery and may be a promising modality to target FLT3 mutations for the development of potent anti-AML drugs. Herein, a kind of FLT3-targeting PROTACs was rationally developed based on a FLT3 inhibitor previously reported by us. The representative co...
Source: European Journal of Medicinal Chemistry - February 22, 2024 Category: Chemistry Authors: Zhijie Wang Xun Lu Canlin Liu Fei Huang Tao Lu Yadong Chen Lifei Liu Shuai Lu Source Type: research

The antibacterial properties of branched peptides based on poly(l-arginine): In vitro antibacterial evaluation and molecular dynamic simulations
In this study, the antibacterial properties of newly synthesized branched poly(l-arginine) peptides, belonging to the family of multiple antigenic peptides, are evaluated. First, in vitro activities of the peptides shows that branched poly(l-arginine) is more efficient than linear poly(l-arginine) containing the same number of arginine residues. Surprisingly, peptides with more arms and more residues are not the most effective. To better understand these unexpected results, interactions between these peptides and the membranes of Gram positive and Gram negative bacteria are simulated thanks to molecular dynamic. It is obse...
Source: European Journal of Medicinal Chemistry - February 22, 2024 Category: Chemistry Authors: Lebaudy Elo ïse Lauriane Petit Yves Nomin é B éatrice Heurtault In ès Ben Hadj Kaddour Bernard Senger Jennifer Rodon Fores Nihal Engin Vrana Florent Barbault Philippe Lavalle Source Type: research