Fig. 5: Pharmacological profiling of 5-nitroimidazole ethers.
a, The PK data of Metro-P3, MF-01, MF-02 and MF-03 in plasma, urine and faeces (dose of 10 mg kg−1 PO, n = 2 mice per compound). b, In vivo efficacy studies in C57BL/6 mice infected with H. pylori SS1 strain and treatment with different regimens: no treatment (n = 7), triple therapies consisting of clarithromycin (7.15 mg kg−1 day−1) and omeprazole (400 µmol kg−1 day−1) with low dose of Metro-P3 (0.02× Metro = 0.30 mg kg−1 day−1; n = 4) or MF-01 (0.02× Metro = 0.30 mg kg−1 day−1; n = 5), standard therapy with Metro (14.2 mg kg−1 day−1, n = 6) or Metro-P3 (1× Metro = 14.2 mg kg−1 day−1, n = 5). The bar charts represent mean values ± s.d. Statistical significance was determined by non-parametric Kruskal–Wallis test with multiple comparisons (no correction) to control column (no treatment). P values: >0.05 (n.s.), ***P < 0.001 (***). The LODs for this assay were calculated as 16.7 CFU mg−1 (SS1) and 15.2 CFU mg−1 (PMSS1), corresponding to one colony on the lowest dilution plated. c, The dual mode of action of 5-nitroimidazole ethers in H. pylori: upon reductive activation, reactive radicals increase stress within the cell, whereas the oxidative stress response is inhibited, eventually leading to H. pylori cell death. The enhanced binding affinity of 5-nitroimidazole ether derivatives to HpTpx led to a 50-fold activity boost in H. pylori in vivo. Schematic in panel c partially created with BioRender.com.
