Showing papers on "Quinolone published in 1994"

Cloning and primary structure of Staphylococcus aureus DNA topoisomerase IV: a primary target of fluoroquinolones

Abstract: A 4.6 kb Staphylococcus aureus DNA fragment containing DNA gyrase-like genes (grlA and grlB) was cloned and sequenced. The proteins GrlA and GrlB exhibit more than 30% identity with E. coli DNA topoisomerase IV subunits and with the gyrase subunits from S. aureus and Escherichia coli. The combined E. coli cell extracts of GrlA and GrlB overproducing strains catalysed ATP-dependent relaxation and decatenation specific to DNA topoisomerase IV. The temperature-sensitive phenotype of Salmonella typhimurium parC and parE mutants was complemented by the S. aureus grlA and grlB genes, when the two genes were co-expressed. These results show that GrlA and GrlB are the subunits of S. aureus DNA topoisomerase IV. The GyrA subunit of DNA gyrase has been previously defined as a primary target of quinolones based on genetic and biochemical experiments essentially carried out in E. coli. Single-point mutations occurring in the 'quinolone resistance-determining region' (QRDR) of GyrA were found in bacteria exhibiting quinolone resistance, the most common mutation being a substitution of Ser-83 on the E. coli GyrA sequence. We analysed eight S. aureus fluoroquinolone-resistant clinical isolates and observed that mutations in the QRDR of GyrA are not present in the low-quinolone-resistant isolates. In contrast, Ser-80 of GrlA, which corresponds to Ser-83 of E. coli GyrA, is substituted to Phe or Tyr in both high- and low-quinolone-resistant isolates. We propose that DNA topoisomerase IV is a primary target of fluoroquinolones in S. aureus.

Association between double mutation in gyrA gene of ciprofloxacin-resistant clinical isolates of Escherichia coli and MICs.

Abstract: The mutations in the quinolone resistance-determining region of the gyrA and gyrB genes from 27 clinical isolates of Escherichia coli with a range of MICs of ciprofloxacin from 0.007 to 128 micrograms/ml and of nalidixic acid from 2 to > 2,000 micrograms/ml were determined by DNA sequencing. All 15 isolates with ciprofloxacin MICs of > or = 1 micrograms/ml showed a change in Ser-83 to Leu of GyrA protein, whereas in clinical isolates with a MIC of > or = 8 micrograms/ml (11 strains), a double change in Ser-83 and Asp-87 was found. All isolates with a MIC of nalidixic acid of > or = 128 micrograms/ml showed a mutation at amino acid codon Ser-83. Only 1 of the 27 clinical isolates of E. coli analyzed showed a change in Lys-447 of the B subunit of DNA gyrase. A change in Ser-83 is sufficient to generate a high level of resistance to nalidixic acid, whereas a second mutation at Asp-87 in the A subunit of DNA gyrase may play a complementary role in developing the strain's high levels of ciprofloxacin resistance.

Mechanisms of quinolone resistance.

Abstract: Two mechanisms of resistance to fluoroquinolones are known: (i) alteration of the molecular target of quinolone action — DNA gyrase, and (ii) reduction of the quinolone accumulation. Mutations altering the N-terminus of the gyrase A subunit, especially those around residues Ser83 and Asp87, significantly reduce the susceptibilities towards all quinolones, while alterations of the gyrase B subunit are rarely found and are of minor importance. Reduced drug accumulation is associated with alterations of the outer membrane protein profile in gram-negative bacteria. Such mutations include the marA locus inEscherichia coli and result in low level resistance towards quinolones and unrelated drugs. Increased activity of naturally existing efflux systems, such as the transmembrane protein NorA of staphylococci, may also lead to reduced accumulation in gram-positive and gram-negative bacteria. Clinical fluoroquinolone resistance is rarely found in intrinsically highly susceptible organisms such asEnterobacteriaceae and involves a combination of at least two mutations. In contrast, species with moderate intrinsic susceptibility such asCampylobacter jejuni, Pseudomonas aeruginosa, andStaphylococcus aureus require only one mutation to become clinically resistant. As a consequence development of resistance during therapy may result from acquisition of already resistant strains in the case of susceptible species, and selection of mutants in the case of less susceptible species.

New quinolones and gram-positive bacteria.

Abstract: The quinolone class of antibacterial agents has evolved rapidly to emerge as one of the most effective classes of drugs in the treatment of infectious diseases. While the spectra and antibacterial activities of fluoroquinolones, such as ciprofloxacin, developed in the 1980s improved to include most gramnegative bacteria, their activities against gram-positive bacteria remained limited. However, the 1990s have seen the synthesis and development of several agents such as sparfloxacin and clinafloxacin (PD127391, C1960, and AM-1091) with good activities for gram-positive bacteria (see Table 1). This article reviews the mechanism of action of quinolones for grampositive bacteria and the mechanisms of resistance by which these organisms evade quinolone action. It focuses on four groups of bacteria: the staphylococci (about which most of the data have been published), the enterococci, the streptococci, and anaerobic gram-positive bacteria.

Interaction of divalent cations, quinolones and bacteria

Abstract: The interaction between divalent cations and quinolones and the mechanism by which the former antagonizes the antimicrobial activities of the latter were investigated. In the presence of either magnesium or calcium chloride, the MICs of 18 quinolones for Gram-positive and Gram-negative bacteria increased. Accumulation of and inhibition of DNA synthesis by quinolones were decreased in the presence of magnesium chloride while, in the presence of EDTA, there was no increase in the concentration of accumulated quinolone for any of the agents tested. Only with nalidixic acid was there enhancement of the inhibition of DNA synthesis. Chelation of selected quinolones by magnesium was demonstrated with a fluorescence assay which showed that the extent to which fluorescence (consistent with chelation) was enhanced varied with the quinolone. Assessment of the strength of the magnesium-quinolone complexes with the chelating agent EDTA demonstrated that some of the complexes could be broken. Thin layer chromatography of quinolones and quinolone-magnesium complexes provided evidence that the components of the complex were probably combined in a ratio of 1:1 and that reduced intracellular accumulation of the quinolones in the presence of magnesium was unlikely to be due to a complex being too bulky to be taken through the porin channels. In contrast with permeabilizers which are known to utilize the self-promoted uptake pathway, none of the quinolones studied permeabilized Gram-negative bacteria to lysozyme, caused enhanced fluorescence to 1-N-phenyl-naphthylamine (NPN) or increased the leakage of periplasmic beta-lactamase into the culture medium. The reduced activities of the quinolones in the presence of divalent cations may be the result of the chelation of exogenous ions and, possibly, lipopolysaccharide- or lipoteichoic acid-associated magnesium ions, thereby resulting in less drug being available to enter the bacterium. Alternatively, reduced activity may be due to a fundamental effect on the interaction between quinolones and their target DNA gyrase.

In vitro susceptibility of Campylobacter and Salmonella isolates from broilers to quinolones, ampicillin, tetracycline, and erythromycin.

Abstract: Summary Recently, an increased resistance of Campylobacter to fluoroquinolones, a newer class of antimicrobial agents in both human and veterinary medicine, has been reported. Campylobacter isolates (617) from 150 broiler flocks were tested for their susceptibility to cephalothin (control), ampicillin, tetracycline, erythromycin, and the quinolones nalidixic acid, flumequine, enrofloxacin, and ciprofloxacin by a disc diffusion method. Almost complete cross‐resistance was found between the quinolones tested. Campylobacter isolates (181, 29%), originating from 55 flocks (37%), were quinolone resistant. Salmonella isolates (94) from 40 flocks were also tested for their antimicrobial susceptibility. Eight isolates (8.5%), from three broiler flocks (7.5%), showed resistance to nalidixic acid and flumequine (and tetracycline), but not to ciprofloxacin or enrofloxacin.

Quinolone resistance in Pseudomonas aeruginosa and Staphylococcus aureus. Development during therapy and clinical significance.

Abstract: This review focuses on published information on the experimental as well as clinical data on the emergence of quinolone resistant isolates. In the course of clinical use of fluoroquinolones, only a sporadic emergence of quinolone resistance has been noted. The resistant organisms emerged particularly in certain clinical settings where large numbers of organisms frequently causing chronic infections are present and/or in loci where quinolone concentrations may not be optimal. In terms of occurrence in individuals, quinolone resistance has emerged most frequently in hospitalized and nursing-home patients with identifiable risk factors. Epidemiological studies revealed that in nearly all the cases studied one or one predominating quinolone resistant clone was selected that was horizontally transmitted. Thus, the emergence of quinolone resistance is not due to an independent selection of resistant strains in a number of patients, but to the clonal spread of one strain once it has acquired quinolone resistance. Therefore, the rate of quinolone resistance is very likely to be lower than reported.

gyrA mutations in quinolone-resistant isolates of the fish pathogen Aeromonas salmonicida.

Abstract: gyrA mutations in quinolone-resistant isolates of Aeromonas salmonicida have been detected by using PCR to amplify the quinolone resistance-determining region of gyrA and subsequent cloning and sequencing of PCR products. Comparison of nucleotide and derived amino acid sequences of PCR products from quinolone-susceptible and -resistant bacteria revealed a serine 83-to-isoleucine substitution in the gyrase A protein of resistant isolates. One of the resistant isolates differed from the other by a two- to fourfold-higher MIC of the fluoroquinolone enrofloxacin and carried an additional alanine 67-to-glycine substitution, which may contribute to the higher level of resistance.

Placement of alkyl substituents on the C-7 piperazine ring of fluoroquinolones: dramatic differential effects on mammalian topoisomerase II and DNA gyrase.

Abstract: quinolone wereprepared andtested inaDNA cleavage assaywithcalf thymus topoisomerase II.Positioning ofthemethyl groups on theC-7piperazineringinfluenced potency against themammalianenzyme;thecis-3,5-dimethyl configuration didnotstimulate cleavage atdrugconcentrations less thanorequal to2,000 ,uM,whilethetrans configuration was active atdruglevels as lowas 36p,M.Removalofthecis-methyl groupsproduced a compound that was onlysixfold less potent thantheantitumor agent etoposide instimulating enzyme-mediated DNA cleavage. Thecis- andtrans-methyl substitutions on thepiperazine thatconferred potency against the mammalian typeII enzyme hadlittle effect on bacterial DNA gyrasecleavage activity, suggesting that an asymmetric barrier exists withthemammalianenzymewhichinfluences productive quinolone interaction, favoring theless bulky trans-3,5-dimethylpiperazine substituent atC-7. Quinolones areantibacterial agents thattarget DNA gyrase(atypeIItopoisomerase) astheir primary mechanism of activity. Thesimilarities inthebiochemical mechanisms and aminoacid sequencesbetweenDNA gyraseandmammalian topoisomerase 11 (6)haveprompted several investigators to determine whetherquinolones couldexhibit potent inhibitoryeffects on theeukaryotic enzyme.Whilethequinolones approved forclinical use as antibacterial agents are not potentinhibitors ofeukaryotic topoisomerase II,theexperimental quinolones CP-115,953 andCP-67,804 haverecently beenshowntoinduceenzyme-mediated DNA cleavage in vitro atconcentrations comparable tothoseoftheanticancer agentetoposide (8,9).Relative activity against themammalian topoisomerase paralleled thecytotoxic potency ofthese novelquinolones against cultured eukaryotic cells (2,8).Our previous studies haveshownthatthe6,8-difluoro-1-cyclopropyl substitution pattern on thequinolone nucleus imparts potenttopoisomerase IIactivity (1,8).Recently, a new 7-(cis-3,5-dimethylpiperazinyl)-6,8-difluoro-5-amino-1-cyclopropyl-substituted quinolone (AT-4140, sparfloxacin) has beendescribed (7). Inour studies, thisquinolone isnot potentatinducing topoisomerase II-mediated DNA cleavage,even though ithasthe6,8-difluoro-1-cyclopropyl structure.Inordertodefine thestructural parameters thatinfluence topoisomerase II potencywithinthisseries, several substituted analogs were prepared andtested ina DNA cleavage assay withenzyme purified fromcalfthymus. Results suggest that an asymmetric barrier thataffects the potencyofquinolones against this eukaryotic topoisomerase II exists on theenzyme.A bulky cis-3,5-dimethyl piperazine substituent attheC-7position inthisseries appears to markedly reducepotencyforinducing enzyme-mediated DNA cleavage. (This workwas presented inpartattheFourth Conference

Fluoroquinolones: antimicrobial agents of the 90’s.

Abstract: The development of fluoroquinolones in early 1980s was a breakthrough in the treatment of infectious diseases. The basic structure of fluoroquinolone consists of quinolone carboxylic acid. The modifications at various positions in structure have resulted in a series of potent compounds having wide spectrum of activity which includes gram negative and gram positive organisms, mycobacterium, chlamydia etc. They act by selective inhibition of bacterial DNA gyrase enzyme. These compounds have proved their utility in the treatment of various infections viz., U.T.I, acute bacterial diarrhoea1 diseases, gonorrhoea, chanchroid, S.typhi infection and various other systemic infections. They also have good prophylactic role in surgery and in immunocompromised patients. Compared to other antimicrobial agents, resistance to fluoroquinolones is not common and in addition, they have fewer and mild side effects like g.i.t disturbances (most frequent), mild CNS reactions (headache, dizziness, sleepiness) and hypersensitivity reactions. The bioavailability of fluoroquinolones is decreased with concomitant administration of antacids, iron salts, ranitidine and pirenzipine. Some of the fluoroquinolones (ciprofloxacin, enoxacin) significantly raise the plasma levels of theophylline and caffeine. Although a large number of fluoroquinolones have been developed in the recent past, yet there is need for compounds which have broader spectrum of activity, higher potency, better CNS/CSF penetration and better patient tolerability.

Synthesis and antitumour activities of tetracyclic quinolone antineoplastic agents.

Abstract: DNA topoisomerases, found in all prokaryotic and eukaryotic cells, play a key role in controlling the topological state of DNA. They are involved in DNA replication, RNA transcription and recombination affecting cell proliferation. Quinolone antibacterial agents have been shown to be inhibitors of DNA gyrase, a bacterial topoisomerase II enzyme. The eukaryotic topoisomerase II is the target of various cytotoxic agents such as adriamycin and etoposide. Due to the mechanistic similarities and sequence homologies shared by both bacterial and mammalian DNA topoisomerase II, we initiated a screening programme to search for quinolones as antitumour agents and reported the identification of a new class of quinolone, quinobenoxazines, having excellent in vitro cytotoxic activity comparable to adriamycin. In the continuation of this research work, we synthesized a series of amino-substituted quinobenoxazines and found that some of them possess more potent in vitro cytotoxicity than the parent unsubstituted quinobenoxazines. The chemical synthesis as well as biological properties of these tetracyclic quinolones are described.

Enhanced chemiluminescence response of polymorphonuclear leukocytes by new quinolone antimicrobials.

Abstract: Some of the many antimicrobial agents (β-lactams, macrolides, aminoglycosides, tetracyclines, new quinolones; NQs) were reported to have a bactericidal or bacteriostatic effect cooperating with host defense mechanisms including polymorphonuclear neutrophils (PMNs). We investigated the effect of new quinolone antimicrobials on chemiluminescence (CL) response of human PMNs. Among many NQs, we chose ofloxacin, lomefloxacin, fleroxacin, sparfloxacin, AM-1155, NM-394, Q-35, Y-26611 and T-3761. Twenty-five or 100 μg/ml of fleroxacin and ofloxacin enhanced luminol-dependent CL response of PMNs up to 1.5-2.0 times compared to the drug free condition. Other antimicrobial agents, however, inhibited CL response. This suggested that fleroxacin and ofloxacin were more efficient in the treatment of bacterial infections with respect to the interaction between antimicrobials and PMNs.

Inhibitory Activity on DNA Gyrase and Intracellular Accumulation of Quinolones : Structure-Activity Relationship of Q-35 Analogs

Abstract: Q-35, 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3- methylaminopiperidine-1-yl)-4-oxyquinoline-3-carboxylic acid, has excellent activity against gram-positive bacteria and inhibits S. aureus gyrase at concentrations more than 10-fold lower than those of other quinolones. In this paper, the effect of the C-7 and C-8 substituents of Q-35 on the inhibitory activity of gyrase purified from S. aureus, M. luteus, E. coli, and P. aeruginosa are described. In addition, intracellular accumulation of Q-35 was examined. The 50% inhibitory concentrations (IC50) of Q-35, 8-fluoro- Q-35, and 8-hydro-Q-35 on DNA gyrase purified from S. aureus were 2.5, 7.8, and 68 micrograms/ml, respectively. The IC50 on gyrase from P. aeruginosa were 11, 5.2, and 17 micrograms/ml, respectively. It is concluded that the introduction of a methoxy group into the 8 position of the quinolone leads to greater antibacterial activity against gram-positive bacteria. The concentrations of Q-35 which accumulated in S. aureus and E. coli were almost equal to ciprofloxacin, but in P. aeruginosa, Q-35 was lower than ciprofloxacin.

Quinolone congeners as mammalian topoisomerase-II inhibitors

Abstract: The development of the quinolone antibacterials has clearly demonstrated that inhibition of topoisomerase activity can constitute an effective means by which to induce selective pathogen cell death. These agents disrupt normal bacterial gyrase protein-DNA substrate interactions and lead to the formation of a ternary \"cleavable complex\" which results in a bactericidp.l therapeutic mode of action. However, certain structural 'subsets' of quinolones have been shown to be toxic to mammalian cells as a result of competing inhibition of mammalian topoisomerase II activity. The investigation of these congeners has revealed that rather simple molecular modifications to the basic quinolone pharmacophore can potentiate activity against mammalian proteins. Structure-activity relationships have been elucidated in an attempt to selectively target the action of mammalian topoisomerase as a means for anticancer chemotherapy.

Activity of twenty-one antimicrobial agents including l-ofloxacin against quinolone-sensitive and -resistant, and methicillin-sensitive and -resistant Staphylococcus aureus.

Abstract: There is a need to identify alternative agents to vancomycin for the treatment of infections with methicillin-resistant Staphylococcus aureus (MRSA). One candidate is the l

Quinolone prophylaxis in neutropenic patients - efficacy versus resistance

Abstract: To assess the efficacy of quinolones in the prophylaxis of infections in neutropenic patients with acute non-lymphocytic leukemia, and to evaluate the emergence of quinolone resistance in two University Hospitals in Brazil, we retrospectively compared 101 consecutive episodes of neutropenia managed with quinolone prophylaxis between 1989 and November 1993, and 26 previous episodes without prophylaxis, and reviewed the results of in vitro sensitivity of Gram-negative strains to quinolones in the same period. Prophylaxis with quinolones resulted in less episodes of bacteremias (21% vs. 69%, p=10(-7)), including Gram-negative bacteremias (6% vs. 38%, p=10(-5)), with no statistically significant difference in the death rate (18% vs. 31%, p=0.14, 95% confidence interval -6-32). The resistance of Gramnegative strains to quinolones rose from 7% to 18% between 1990 and 1993 (p=10(-5)). The resistance against ceftazidime and amikacin, the agents used in the empirical antibiotic therapy, increased in the same proportion as the quinolones. Given the limited benefit of quinolones as prophylaxis and the increasing number of quinolone-resistant Gram-negative strains observed in our hospitals, the use of quinolones as prophylaxis must be seriously questioned. A stricter control of the use of quinolones in these hospitals might decrease resistance.

Recent Progress in the Studies of Quinolone Antibacterials

Abstract: Nalidixic acid is a synthetic antibacterial agent active against Gram-negative organism. Since the introduction of Nalidixic acid in 1962, a large number of quinolone carboxylic acids have been synthesized. Early in the 1980's new agents such as norfloxacin, enoxacin, ofloxacin and ciprofloxacin, possessing the 6-fluoro substituent and the 7-piperazinyl group on the quinolone pharmacophore and collectively known as new quinolones or fluoroquinolones, were reported to have greatly improved potency and antibacterial spectra relative to old quinolones.Subsequently, considerable interest has been increasingly given to the structural manipulation of substituents on quinolone nucleus and detailed data for structure-activity relationships have been accumulated. This review will focus primarily on the recent advance in medicinal chemical studies of new quinolones in consideration of in vitro antibacterial activity, pharmacological properties, and physicochemical properties.

Antagonism between bactericidal activities of 4-quinolones and coumarins gives insight into 4-quinolone killing mechanisms.

Abstract: At concentrations exceeding their MICs, novobiocin and coumermycin antagonised the bactericidal activities of nalidixic acid, ciprofloxacin, ofloxacin and norfloxacin against Escherichia coli KL16. The sensitivities to killing by ciprofloxacin of four mutant derivatives of KL16 carrying gyrA, nalB, nal24 or nal31 alleles were also antagonised by novobiocin. The activities of drug combinations were tested in nutrient broth, which allowed expression of 4-quinolone killing mechanisms A, B and C. They were also tested in nutrient broth plus rifampicin to inhibit mechanisms A and C of the 4-quinolones, and in phosphate-buffered saline, which inhibited mechanism A. Results showed that novobiocin antagonised mechanism C, but not B, of both ciprofloxacin and ofloxacin, but did not antagonise mechanism C of norfloxacin. A review of these and other data indicates that mechanism B may result from the activities of SOS error-prone DNA repair on an irreversibly-bound drug-gyrase-DNA complex, and that mechanism C is mediated via drug interaction with the B subunit of DNA gyrase.

[Quinolone-resistant Escherichia coli in the health area of a 650-bed hospital].

Abstract: Report of a retrospective study to evaluate susceptibility of Escherichia coli to quinolones covering the March-December 1992 interval. During this time, intra and extra-hospital strains were indistinctly studied in patients with urinary infections seen in a health district serving a total of 200.000 inhabitants. Resistance to Pipemidic acid, Norfloxacin and Ciprofloxacin was evaluated. The values found were 14.8% resistance to Pipemidic acid, 11.1% to Norfloxacin and 8.5% to Ciprofloxacin. It seems necessary to develop and apply methods addressed to minimize the appearance of quinolone resistance, which should be implemented in order to preserve the usefulness of these drugs.

Transition-Metal-Mediated Cytotoxicity of Quinolones to L1210 Cells

Abstract: Transition metals tested, , and , were found effective in the induction of the cytotoxicity of the quinolones tested, nalidixic acid, oxolinic acid, and pipemidic acid, against L1210 leukemia cells in vitro, whereas the alkaline earth metal, , was not. The differential effect of the metals on the quinolone cytotoxicity can be explained by their different mode of interaction with the quinolones. Our present difference spectroscopic titration data suggest that the transition metals can form DNA-intercalating agents, with the quinolones, which can cause the cytotoxicity.

Chapter 12. Antibacterial Agents

Abstract: Publisher Summary El101, the isopropoxycarbonyloxyethyl ester prodrug of El100, exhibits good oral absorption, and has potent activity against susceptible strains. Among carbapenems, most new agents contain the 18-methyl group that has been found to impart good stability to renal dehydropeptidase I. The majority of the currently marketed quinolones, such as ciprofloxacin, contain a piperazine or substituted piperazine at the 7-position. These agents are used for a broad variety of clinical indications, such as respiratory tract, urinary tract, skin and soft tissue, bone, and sexually transmitted diseases. Methyl substitution on the pyrrolidine ring is found to improve the solubility and, therefore, provide a better pharmacokinetic profile. Mechanism of action studies against E. coli suggest that, while intact cephalosporin 3'-quinolone esters act as cephalosporins, carbarnates and amines may possess both cephalosporin and quinolone activity in the intact molecule. The 8a-azalides exhibit improved acid stability and comparable activity in mouse infection models. Glycylcycline is a new series of tetracycline derivatives, found to have a broad spectrum of activity against tetracycline susceptible and resistant bacteria, including strains containing ribosomal protection resistance determinants. Some of these analogs exhibit good activity against streptococcal and enterococcal strains that are resistant to vancomycin. Replacement of the dehydrofucose sugar moiety, with an allyl group, affords activity comparable to that of the natural product.

Recent Progress in the Studies of Quinolone Antibacterials

Abstract: Nalidixic acid is a synthetic antibacterial agent active against Gram-negative organism. Since the introduction of Nalidixic acid in 1962, a large number of quinolone carboxylic acids have been synthesized. Early in the 1980's new agents such as norfloxacin, enoxacin, ofloxacin and ciprofloxacin, possessing the 6-fluoro substituent and the 7-piperazinyl group on the quinolone pharmacophore and collectively known as new quinolones or fluoroquinolones, were reported to have greatly improved potency and antibacterial spectra relative to old quinolones.Subsequently, considerable interest has been increasingly given to the structural manipulation of substituents on quinolone nucleus and detailed data for structure-activity relationships have been accumulated. This review will focus primarily on the recent advance in medicinal chemical studies of new quinolones in consideration of in vitro antibacterial activity, pharmacological properties, and physicochemical properties.

Hybrid Antibiotics: Aminoglycoside 3-Quinolone or β-Lactam Amides

Abstract: A wide variety of derivatives of aminoglycosides have been prepared over many years, in the effort to improve the antibacterial activity and decrease their toxicity [1].