Open AccessCompound 64716, a New Synthetic Antibacterial Agent
Author(s) -
Warren E. Wick,
David A. Preston,
W. White,
Robert S. Gordee
Publication year - 1973
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.4.4.415
Subject(s) - nalidixic acid , antibacterial activity , bacteria , oxolinic acid , microbiology and biotechnology , minimum inhibitory concentration , escherichia coli , antibacterial agent , chemistry , in vivo , minimum bactericidal concentration , antimicrobial , pharmacology , antibiotics , biology , biochemistry , antibiotic resistance , genetics , gene
Compound 64716, 1-ethyl-4 (1H)-oxo-[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid, is a new synthetic antibacterial agent. The antibacterial spectrum of this compound includes gram-negative bacteria that are most frequently isolated from urinary tract infections. Minimal inhibitory concentration values of 64716 for isolates ofEscherichia coli andProteus sp. ranged from 2 to 4 and 2 to 8 μg/ml, respectively, and the compound was bactericidal at concentrations close to the minimal inhibitory concentration values. In vivo, doses required for successful therapy of experimental mouse infections were comparable to those for nalidixic acid. After oral administration of 40 mg/kg, peak concentrations of this compound in mouse blood reached 19.2 μg/ml. Within 30 min after doses of 20 mg/kg, bacteriologically active drug concentrations of 64716, nalidixic acid, and oxolinic acid in mouse urine were >1,000, 170, and <1.5 μg/ml, respectively. Resistant bacteria were not selected when bacteria were exposed to 500 μg/ml of 64716. Compound 64716 was less bound by human serum proteins than was nalidixic acid. Equivalent antibacterial activity along with superior pharmacological properties of 64716 when compared with nalidixic acid lead to the conclusion that this new compound is a promising antibacterial agent.