RRC ID 55190
Author Ohishi T, Masuda T, Abe H, Hayashi C, Adachi H, Ohba SI, Igarashi M, Watanabe T, Mimuro H, Amalia E, Inaoka DK, Mochizuki K, Kita K, Shibasaki M, Kawada M.
Title Monotherapy with a novel intervenolin derivative, AS-1934, is an effective treatment for Helicobacter pylori infection.
Journal Helicobacter
Abstract BACKGROUND:Helicobacter pylori (H. pylori) infection causes various gastrointestinal diseases including gastric cancer. Hence, eradication of this infection could prevent these diseases. The most popular first-line treatment protocol to eradicate H. pylori is termed "triple therapy" and consists of a proton pump inhibitor (PPI), clarithromycin, and amoxicillin or metronidazole. However, the antibiotics used to treat H. pylori infection are hindered by the antibiotics-resistant bacteria and by their antimicrobial activity against intestinal bacteria, leading to side effects. Therefore, an alternative treatment with fewer adverse side effects is urgently required to improve the overall eradication rate of H. pylori.
OBJECTIVE:The aim of this study was to assess the effectiveness and mechanism of action of an antitumor agent, intervenolin, and its derivatives as an agent for the treatment of H. pylori infection.
RESULTS:We demonstrate that intervenolin, and its derivatives showed selective anti-H. pylori activity, including antibiotic-resistant strains, without any effect on intestinal bacteria. We showed that dihydroorotate dehydrogenase, a key enzyme for de novo pyrimidine biosynthesis, is a target and treatment with intervenolin or its derivatives decreased the protein and mRNA levels of H. pylori urease, which protects H. pylori against acidic conditions in the stomach. Using a mouse model of H. pylori infection, oral monotherapy with the intervenolin derivative AS-1934 had a stronger anti-H. pylori effect than the triple therapy commonly used worldwide to eradicate H. pylori.
CONCLUSION:AS-1934 has potential advantages over current treatment options for H. pylori infection.
Volume 23(2)
Pages e12470
Published 2018-4-1
DOI 10.1111/hel.12470
PMID 29488678
IF 3.352
Times Cited 6
Resource
General Microbes JCM 12093 JCM 12095 JCM 5803 JCM 5804 JCM 5825 JCM 11019 JCM 9497 JCM 5824 JCM 5827 JCM 5828 JCM 5826 JCM 12986 JCM 1251 JCM 7096 JCM 1209 JCM 1192 JCM 1222 JCM 10188 JCM 9979 JCM 6421 JCM 17463 JCM 6320 JCM 1132 JCM 1173 JCM 1131 JCM 1149 JCM 1772 JCM 1769 JCM 1471 JCM 14656 JCM 14655 JCM 12972 JCM 5803 JCM 5804 JCM 1386 JCM 1391 JCM 1395 JCM 1296 JCM 1380 JCM 1292 JCM 1427 JCM 1298