Synthesis of 3-O-demethylfortimicins

Martin, Jerry R.; Johnson, Paulette; Tadanier, Jack; Goldstein, Alma W.

doi:10.1128/aac.18.5.761

Cited by 17 publications

(3 citation statements)

References 10 publications

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“…K-4619 was approximately four times more effective than sporaricin A against P. aeruginosa, suggesting that the 3-hydroxy group has a predominant role in the antipseudomonal activity of K-4619. Similar results have been observed with the 3-de-O-methyl derivatives of fortimicin A and istamycins A and B (2)(3)(4)(5)8).…”

supporting

confidence: 75%

In vitro and in vivo antibacterial activities of K-4619, a new semisynthetic aminoglycoside

Saino¹,

Hattori²,

Koshi³

et al. 1984

Antimicrob Agents Chemother

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The antibacterial activities of K-4619 (3-de-O-methylsporaricin A sulfate) were compared with those of sporaricin A, amikacin, dibekacin, and gentamicin. K-4619 exhibited a high order of activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. Its activity against Providencia species and Serratia marcescens was the highest of all drugs tested. K-4619 was highly effective against bacteria that produce various aminoglycoside-inactivating enzymes, except for 3-acetyltransferase I. The bactericidal activity of K-4619 was somewhat greater than that of amikacin. The activity of K-4619 against gram-negative bacteria increased at alkaline pH and was hardly affected by inoculum size, addition of horse serum, and composition of the medium. The in vivo protective effect of K-4619 against infections with Klebsiella pneumoniae, S. marcescens, and P. aeruginosa in mice was greater than that of sporaricin A. K-4619 was also active in mice infected with gentamicin- or amikacin-resistant strains bearing some of the aminoglycoside-inactivating enzymes.

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supporting

confidence: 75%

In vitro and in vivo antibacterial activities of K-4619, a new semisynthetic aminoglycoside

Saino¹,

Hattori²,

Koshi³

et al. 1984

Antimicrob Agents Chemother

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“…In an attempt to improve the activity and/or broaden the antimicrobial spectrum of this antibiotic, a number of modified fortimicins have been prepared (9). This study reports on the in vitro and in vivo antimicrobial properties of 3-O-demethylfortimicin A (ODMF), a derivative of fortimicin A with improved antibacterial activity (8 index is the sum of the fractional inhibitory concentrations of the individual antibiotics at the most effective combination, i.e., that for which the sum is minimal.…”

mentioning

confidence: 99%

Comparative antimicrobial activity of O-demethylfortimicin A, a derivative of fortimicin A

Girolami¹,

Stamm²

1980

Antimicrob Agents Chemother

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The in vitro antimicrobial activity of O-demethylfortimicin A (ODMF), a derivative of fortimicin A, was compared with those of fortimicin A and gentamicin against a spectrum of 256 organisms. All three antibiotics were active in low concentrations against all strains of Enterobacteriaceae, Acinetobacter sp., and Staphylococcus aureus, with ODMF most active against Proteus mirabilis, indole-positive Proteus, and Providencia and gentamicin most active against other species. Activity of each of the antibiotics against group D streptococci was poor. The overall activity of ODMF was superior to that of fortimicin A for all groups of organisms examined and was most pronounced, approximately three-fold, against strains of Pseudomonas aeruginosa. Both ODMF and fortimicin A were resistant to the action of several aminoglycoside-inactivating enzymes, with the exception of 3-N-acetyltransferase-I. ODMF and fortimicin A showed similar rapid bactericidal effects at multiples of the minimum inhibitory concentration and equivalent synergistic activity against enterococci when combined with penicillin G. The combination of carbenicillin with ODMF, fortimicin A, or gentamicin was synergistic for approximately 80% of the P. aeruginosa strains tested. Inactivation of ODMF and fortimicin A when combined with carbenicillin in vitro was minimal or absent, whereas gentamicin was substantially inactivated under similar conditions. ODMF, fortimicin A, and gentamicin exhibited protective activity in mice infected with Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, S. aureus, or P. aeruginosa. Gentamicin was the most active, followed by ODMF and fortimicin A. The superior in vitro activity of ODMF compared with fortimicin A against P. aeruginosa was confirmed in vivo.

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“…Because of the great diversity of macrolide structures and the wide range of producing organisms the number of conceivable biosynthetic permutations is enormous. Mutants blocked in various stages of the biosynthetic pathway have been valuable in elucidating the sequence of biosynthetic events (Martin & Rosenbrook, 1968;Martin & Goldstein, 1970) and in generating novel macrolide derivatives (LeMahieu et al, 1976). Omura et al (1980) successfully used the fatty acid synthesis condensing enzyme inhibitor cerulenin to block aglycone formation in the pikromycin (14-membered macrolide) producing organism and then incubating it with protylonide, the 16-membered aglycone tylosin, to give a 16-membered macrolide with desosamine as its sugar.…”

Section: Macrolidesmentioning

confidence: 99%

Enzymatic and Microbial Transformation of Antibiotics and Steroids

O'Sullivan

1990

Microbial Enzymes and Biotechnology

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Synthesis of 3-O-demethylfortimicins

Cited by 17 publications

References 10 publications

In vitro and in vivo antibacterial activities of K-4619, a new semisynthetic aminoglycoside

In vitro and in vivo antibacterial activities of K-4619, a new semisynthetic aminoglycoside

Comparative antimicrobial activity of O-demethylfortimicin A, a derivative of fortimicin A

Enzymatic and Microbial Transformation of Antibiotics and Steroids

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