ArticleAntimicrobial agents and chemotherapy1995
Mechanism of action of antimycobacterial activity of the new benzoxazinorifamycin KRM-1648.
Article in Antimicrobial agents and chemotherapy, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 33 citations in OpenAlex.
- Inhibition of RNA Polymerase by Rifampicin and Rifamycin-Like Molecules.EcoSal Plus · 2020Article
- Co-evolution of RNA polymerase with RbpA in the phylum Actinobacteria.Applied & translational genomics · 2012Article
- Antimicrobial susceptibility testing, drug resistance mechanisms, and therapy of infections with nontuberculous mycobacteria.Clinical microbiology reviews · 2012Review
- Efficacy of benzoxazinorifamycins in a mouse model of Chlamydia pneumoniae lung infection.Antimicrobial agents and chemotherapy · 2008Article
- Efficacy of novel rifamycin derivatives against rifamycin-sensitive and -resistant Staphylococcus aureus isolates in murine models of infection.Antimicrobial agents and chemotherapy · 2006Article
- Rifalazil pretreatment of mammalian cell cultures prevents subsequent Chlamydia infection.Antimicrobial agents and chemotherapy · 2006Article
- Rifalazil treats and prevents relapse of clostridium difficile-associated diarrhea in hamsters.Antimicrobial agents and chemotherapy · 2004Article
- In vitro anti-Helicobacter pylori activities of new rifamycin derivatives, KRM-1648 and KRM-1657.Antimicrobial agents and chemotherapy · 1999Article
- Anticytomegaloviral activity of methotrexate associated with preferential accumulation of drug by cytomegalovirus-infected cells.Antimicrobial agents and chemotherapy · 1996Article
- How effective is KRM-1648 in treatment of disseminated Mycobacterium avium complex infections in beige mice?Antimicrobial agents and chemotherapy · 1996Article
- In vitro and in vivo activities of the benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 1995Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanism of antimicrobial activity of KRM-1648 (KRM), a new rifamycin derivative with potent antimycobacterial activity, was studied. Both KRM and rifampin (RMP) inhibited RNA polymerases from Escherichia coli and Mycobacterium avium at low concentrations: the 50% inhibitory concentrations (IC50s) of KRM and RMP for E. coli RNA polymerase were 0.13 and 0.10 micrograms/ml, respectively, while the IC50s for M. avium RNA polymerase were 0.20 and 0.07 microgram/ml. Both KRM and RMP exerted weak inhibitory activity against Mycobacterium fortuitum RNA polymerase, rabbit thymus RNA polymerases, E. coli DNA polymerase I, and two types of reverse transcriptases. Uptake of 14C-KRM by M. avium reached 18,000 dpm/mg (dry weight) 1.5 h after incubation, while uptake by E. coli cells was slight. KRM was much more effective in inhibiting uptake of 14C-uracil than was RMP (IC50 of KRM, 0.04 microgram/ml; IC50 of RMP, 0.12 microgram/ml). These findings suggest, first, that the potent antimycobacterial activity of KRM is due to inhibition of bacterial RNA polymerase and, second, that the activity of KRM against target organisms depends on target cell wall permeability.
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