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A series of novel 4‐bromo‐1H‐indazole derivatives as filamentous temperature‐sensitive protein Z (FtsZ) inhibitors were designed, synthesized, and assayed for their in vitro antibacterial activity against various phenotypes of Gram‐positive and Gram‐negative bacteria and their cell division inhibitory activity. The results indicated that this series showed better antibacterial activity against Staphylococcus epidermidis and penicillin‐susceptible Streptococcus pyogenes than the other tested strains. Among them, compounds 12 and 18 exhibited 256‐fold and 256‐fold more potent activity than 3‐methoxybenzamide (3‐MBA) against penicillin‐resistant Staphylococcus aureus, and compound 18 showed 64‐fold better activity than 3‐MBA but 4‐fold weaker activity than ciprofloxacin in the inhibition of S. aureus ATCC29213. Particularly, compound 9 presented the best activity (4 µg/mL) against S. pyogenes PS, being 32‐fold, 32‐fold, and 2‐fold more active than 3‐MBA, curcumin, and ciprofloxacin, respectively, but it was four times less active than oxacillin sodium. In addition, some synthesized compounds displayed moderate inhibition of cell division against S. aureus ATCC25923, Escherichia coli ATCC25922, and Pseudomonas aeruginosa ATCC27853, sharing a minimum cell division concentration of 128 µg/mL.
Novel 4‐bromo‐1H‐indazole derivatives were designed as filamentous temperature‐sensitive protein Z (FtsZ) inhibitors. Compound 18 exhibited 256‐fold and 64‐fold more potent activity than 3‐methoxybenzamide against S. aureus PR and S. aureus ATCC29213, respectively. Besides, compound 18 showed a minimum cell division concentration of 128 μg/mL, indicating its good on‐target activity as FtsZ inhibitor.
Abstract The single radial immunodiffusion assay has been the accepted method for determining the potency of inactivated influenza vaccines since 1978. The world‐wide adoption of this assay for vaccine standardisation was facilitated through collaborative studies that demonstrated a high ... mehr
Abstract Background Whether morbidity from the 1918‐19 influenza pandemic discriminated by socioeconomic status has remained a subject of debate for 100 years. In lack of data to study this issue recent literature have hypothesized that morbidity was “socially neutral”. Objectives ... mehr