Mechanism of action of antimycobacterial activity of the new benzoxazinorifamycin KRM-1648.

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Fujii K, Saito H, Tomioka H, Mae T, Hosoe K

Mechanism of action of antimycobacterial activity of the new benzoxazinorifamycin KRM-1648.

Antimicrob Agents Chemother. 1995 Jul;39(7):1489-92.

PubMed ID

7492091 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Rifalazil	DNA-directed RNA polymerase subunit beta	Protein	Escherichia coli (strain K12)	Unknown	Not Available	Details