Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes a crucial step in the biosynthesis of guanine nucleotides. Being a validated target for immunosuppressive, antiviral, and anticancer drug development, lately it has been exploited as a promising target for antimicrobial therapy. Extending our previous work on Mycobacterium tuberculosis IMPDH, GuaB2, inhibitor development, we screened a set of 23 new chemical entities (NCEs) with substituted flavone (Series 1) and 1,2,3-triazole (Series 2) core structures for their in vitro Helicobacter pylori IMPDH (HpIMPDH) and human IMPDH2 (hIMPDH2) inhibitory activities. All the NCEs possessed acceptable molecular, physicochemical, and toxicity property profiles. The ranges for HpIMPDH and hIMPDH2 inhibition were 9-99.9% and 16-57%, respectively, at 10 μM concentration. The most potent HpIMPDH inhibitor, 25c, exhibited IC value of 1.27 μM with no hIMPDH2 inhibitory activity. The moderately potent, structurally novel hit molecule, 25c, may serve as a lead for further design and development of highly potent HpIMPDH inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/ddr.21467 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Innovative nomogram approach to enhance the prediction of Helicobacter pylori infection in children via magnetic-controlled capsule endoscopy.
Eur J Pediatr
January 2025
Department of Digestive Endoscopy Center, School of Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China.
Unlabelled: Early detection and intervention are crucial in managing Helicobacter pylori (HP) infections, which are associated with various gastrointestinal diseases in children. The traditional Kyoto gastritis scoring system, though effective, requires adaptation for non-invasive techniques like magnetic-controlled capsule endoscopy to enhance early diagnosis and improve patient comfort. This retrospective study involved 474 pediatric patients who underwent magnetic-controlled capsule endoscopy coupled with a C urea breath test at the Children's Hospital affiliated with Shanghai Jiao Tong University School of Medicine from January to December 2023.
View Article and Find Full Text PDFFunctional dyspepsia (FD) is a gut-brain axis disorder characterized by postprandial fullness, early satiety, bloating and/or epigastric pain, which are presumed to originate in the gastroduodenal tract. While the international recommendations in the Rome IV consensus require endoscopy to rule out an organic condition before establishing a diagnosis of FD, international guidelines recommend that, in the absence of risk factors, patient management be initiated at the primary care level by establishing Helicobacter pylori infection status, with eradication when positive, followed by empiric therapy with proton pump inhibitors and/or prokinetics, and that endoscopy be reserved for patients refractory to said measures. Second-line therapy includes neuromodulating agents, among which tricyclic antidepressants and atypical antipsychotics such as levosulpiride stand out.
View Article and Find Full Text PDFRelationship between infection and gastroesophageal reflux disease.
Prz Gastroenterol
December 2024
Department of Pathology, Detagen Pathology Laboratory, Kayseri, Turkey.
Introduction: Gastroesophageal reflux disease (GERD) is a common disease that negatively affects the quality of life, and its pathophysiology is multifactorial.
Aim: Our study aims to investigate the relationship between histological and topographic characteristics of () gastritis and the symptoms, presence, and severity of oesophagitis in patients with reflux symptoms.
Material And Methods: The symptoms, demographic data, and physical examination results of the patients admitted with gastrointestinal complaints were recorded and oesophagogastroduodenoscopies were performed.
Helicobacter pylori CagA promotes gastric cancer immune escape by upregulating SQLE.
Cell Death Dis
January 2025
Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory for Digestive Health, National Clinical Research Center of Digestive Diseases, Beijing Digestive Disease Center, Beijing, 100050, China.
Helicobacter pylori (H. pylori) infection is a well-established risk factor for gastric cancer, primarily due to its virulence factor, cytotoxin-associated gene A (CagA). Although PD-L1/PD-1-mediated immune evasion is critical in cancer development, the impact of CagA on PD-L1 regulation remains unclear.
View Article and Find Full Text PDFAltered Cytokine Production in Patients with Infection.
Middle East J Dig Dis
October 2024
Department of Laboratory Sciences, School of Allied Medical Sciences, Ahvaze Jundishapur University of Medical Sciences, Ahvaz, Iran.
Background: is a gram-negative pathogen. The infection caused by this pathogen may result in gastritis and can increase the risk of gastric cancer. This study investigated the relationship between infection as the main risk factor for gastritis and changes in serum inflammatory cytokine levels.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!