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 strategies based on natural products and synthetic derivatives to overcome resistance in Mycobacterium tuberculosis
Eur J Med Chem. 2024 Feb 23;269:116268. doi: 10.1016/j.ejmech.2024.116268. Online ahead of print.ABSTRACTOne of the biggest health challenges of today's world is the emergence of antimicrobial resistance (AMR), which renders conventional therapeutics insufficient and urgently demands the generation of novel antimicrobial strategies. Mycobacterium tuberculosis (M. tuberculosis), the pathogen causing tuberculosis (TB), is among the most successful bacteria producing drug-resistant infections. The versatility of M. tuberculosis allows it to evade traditional anti-TB agents through various acquired and intrinsic mechanisms, re...
Source: European Journal of Medicinal Chemistry - March 9, 2024 Category: Chemistry Authors: Adelina-Gabriela Niculescu Georgiana Ramona M ük Speranta Avram Ilinca Margareta Vlad Carmen Limban Diana Nuta Alexandru Mihai Grumezescu Mariana-Carmen Chifiriuc Source Type: research

Synthesis and preliminary anticancer evaluation of photo-responsive prodrugs of hydroxymethylene bisphosphonate alendronate
We describe in this article the synthesis of light-responsive prodrugs of HMBP alendronate. These prodrugs include lipophilic photo-removable nitroveratryl groups which partially mask the highly polar alendronate HMBP scaffold. Photo-responsive prodrugs of alendronate are stable in physiological conditions and display reduced toxicity compared to alendronate against MDA-MB-231 cancer cells. However, the antiproliferative effect of these prodrugs is efficiently restored after cleavage of their nitroveratryl groups upon exposure to UV light. In addition, substitution of alendronate with such photo-responsive substituents dra...
Source: European Journal of Medicinal Chemistry - March 9, 2024 Category: Chemistry Authors: Aur élie Descamps Philippe Arnoux C éline Frochot Florent Barbault Julia Deschamp Maelle Monteil Evelyne Migianu-Griffoni Thibaut Legigan Marc Lecouvey Source Type: research

Structure-based discovery of potent CARM1 inhibitors for colorectal cancer therapy
This study provides valuable insights for the future development of specific and effective CARM1 inhibitors.PMID:38460270 | DOI:10.1016/j.ejmech.2024.116288 (Source: European Journal of Medicinal Chemistry)
Source: European Journal of Medicinal Chemistry - March 9, 2024 Category: Chemistry Authors: Chenyu Liu Yang Li Zhihao Liu Chenxi Cao Min Lin Xin Chen Mengting Yuan Yaohua Fan Xiaodong Gu Lei Wang Fan Yang Fei Ye Jia Jin Source Type: research

Novel thiazolidin-4-one benzenesulfonamide hybrids as PPAR γ agonists: Design, synthesis and in vivo anti-diabetic evaluation
Eur J Med Chem. 2024 Feb 29;269:116279. doi: 10.1016/j.ejmech.2024.116279. Online ahead of print.ABSTRACTIn the current study, two series of novel thiazolidin-4-one benzenesulfonamide arylidene hybrids 9a-l and 10a-f were designed, synthesized and tested in vitro for their PPARɣ agonistic activity. The phenethyl thiazolidin-4-one sulphonamide 9l showed the highest PPARɣ activation % by 41.7%. Whereas, the 3-methoxy- and 4-methyl-4-benzyloxy thiazolidin-4-one sulphonamides 9i, and 9k revealed moderate PPARɣ activation % of 31.7, and 32.8%, respectively, in addition, the 3-methoxy-3-benzyloxy thiazolidin-4-one sulphonamid...
Source: European Journal of Medicinal Chemistry - March 9, 2024 Category: Chemistry Authors: Islam H Ali Rasha M Hassan Ahmed M El Kerdawy Mahmoud T Abo-Elfadl Heba M I Abdallah Francesca Sciandra Iman A Y Ghannam Source Type: research

Unlocking the potential of 1,4-naphthoquinones: A comprehensive review of their anticancer properties
Eur J Med Chem. 2024 Feb 23;268:116249. doi: 10.1016/j.ejmech.2024.116249. Online ahead of print.ABSTRACTCancer encompasses a group of pathologies with common characteristics, high incidence, and prevalence in all countries. Although there are treatments available for this disease, they are not always effective or safe, often failing to achieve the desired results. This is why it is necessary to continue the search for new therapies. One of the strategies for obtaining new antitumor drugs is the use of 1,4-naphthoquinone as a scaffold in synthetic or natural products with antitumor activity. This review focuses on compilin...
Source: European Journal of Medicinal Chemistry - March 8, 2024 Category: Chemistry Authors: Eduardo Angulo-Elizari Andreina Henriquez-Figuereo Cristina Mor án-Serradilla Daniel Plano Carmen Sanmart ín Source Type: research

Biochemical and structural characterization of chlorhexidine as an ATP-assisted inhibitor against type 1 methionyl-tRNA synthetase from Gram-positive bacteria
Eur J Med Chem. 2024 Mar 4;268:116303. doi: 10.1016/j.ejmech.2024.116303. Online ahead of print.ABSTRACTMethionyl-tRNA synthetase (MetRS) catalyzes the attachment of l-methionine (l-Met) to tRNAMet to generate methionyl-tRNAMet, an essential substrate for protein translation within ribosome. Owing to its indispensable biological function and the structural discrepancies with human counterpart, bacterial MetRS is considered an ideal target for developing antibacterials. Herein, chlorhexidine (CHX) was identified as a potent binder of Staphylococcus aureus MetRS (SaMetRS) through an ATP-aided affinity screening. The co-cryst...
Source: European Journal of Medicinal Chemistry - March 8, 2024 Category: Chemistry Authors: Feihu Lu Kaijiang Xia Jingtian Su Jia Yi Zhiteng Luo Jun Xu Qiong Gu Bingyi Chen Huihao Zhou Source Type: research

Discovery of 2,9-diaryl-6-carbamoylpurines as a novel class of antitubercular agents
Eur J Med Chem. 2024 Mar 2;268:116297. doi: 10.1016/j.ejmech.2024.116297. Online ahead of print.ABSTRACTA series of novel 9-alkyl/aryl-2-aryl-6-carbamoylpurines were synthesized, and their activity against Mycobacterium tuberculosis strain H37Rv was assessed. The SAR analysis on the first set of derivatives, with an alkyl or aryl unit at N-9 and a phenolic unit at C-2, showed that the activity depends on the purine ring substituents at N-9 and C-2. A phenyl group at N-9 combined with a 3-hydroxyphenyl or 4-hydroxyphenyl at C-2 improve the activity. The most active compound of this set has a phenyl group at N-9 and a 4-hydr...
Source: European Journal of Medicinal Chemistry - March 8, 2024 Category: Chemistry Authors: Carla Correia Ana Cla údia Leite Alexandra G Fraga M Fernanda Proen ça Jorge Pedrosa M Alice Carvalho Source Type: research

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