319-40-4Relevant articles and documents
Structure-Activity Study of Nitazoxanide Derivatives as Novel STAT3 Pathway Inhibitors
Lü, Zirui,Li, Xiaona,Li, Kebin,Wang, Cong,Du, Tingting,Huang, Wei,Ji, Ming,Li, Changhong,Xu, Fengrong,Xu, Ping,Niu, Yan
supporting information, p. 696 - 703 (2021/05/04)
We identified nitazoxanide (NTZ) as a moderate STAT3 pathway inhibitor through immunoblot analysis and a cell-based IL-6/JAK/STAT3 pathway activation assay. A series of thiazolide derivatives were designed and synthesized to further validate the thiazolide scaffold as STAT3 inhibitors. Eight out of 25 derivatives displayed potencies greater than that of NTZ, and their STAT3 pathway inhibitory activities were found to be significantly correlated with their antiproliferative activities in HeLa cells. Derivatives 15 and 24 were observed to be more potent than the positive control WP1066, which is under phase I clinical trials. Compared with NTZ, 15 also exhibited much improved in vivo pharmacokinetic parameters in rats and efficacies against proliferations in multiple cancer cell lines, indicating a broad-spectrum effect of these thiazolides as antitumor agents targeted on STAT3.
Synthesis and Antimicrobial Evaluation of Nitazoxanide-Based Analogues: Identification of Selective and Broad Spectrum Activity
Ballard, T. Eric,Wang, Xia,Olekhnovich, Igor,Koerner, Taylor,Seymour, Craig,Salamoun, Joseph,Warthan, Michelle,Hoffman, Paul S.,Macdonald, Timothy L.
experimental part, p. 362 - 377 (2012/01/11)
A library composed of nitazoxanide-based analogues was synthesized and assayed for increased antibacterial efficacy against the pyruvate-ferredoxin oxidoreductase (PFOR) using microorganisms Helicobacter pylori, Campylobacter jejuni and Clostridium difficile. Derivatives were found to recapitulate and improve activity against these organisms and select analogues were tested for their ability to disrupt the PFOR enzyme directly. The library was also screened for activity against staphylococci and resulted in the identification of analogues capable of inhibiting both staphylococci and all PFOR organisms at low micromolar minimum inhibitory concentrations with low toxicity to human foreskin cells. Hitting them where it hurts! A library of nitazoxanide-based analogues was synthesized and assayed for antibacterial efficacy against pyruvate-ferredoxin oxidoreductase (PFOR) utilizing microorganisms. Derivatives were found to recapitulate and improve activity against these organisms, and select analogues were screened for activity against staphylococci resulting in the identification of analogues capable of inhibiting both staphylococci and all PFOR organisms at low micromolar minimum inhibitory concentrations.
