bekanamycin and Bacterial-Infections

Infections especially tuberculosis caused by various bacteria including mycobacteria result in millions of lives every year, but the control of bacterial infections is challenged by the limitation of effective pharmaceuticals against drug-resistant pathogens. Nitroimidazoles belong to a group of nitroheterocyclic compounds that have broad-spectrum activity against a series of organisms such as mycobacteria, anaerobic Gram-positive and Gram-negative bacteria, and some of them have already been used in clinics or under clinical trials for the treatment of infectious diseases. In this review, we made an overview of the recent advances in nitroimidazole-containing compounds with antibacterial and antitubercular activity in the recent 20 years.

Topics: Anti-Bacterial Agents; Bacterial Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Molecular Structure; Nitroimidazoles

Cationic amphiphiles derived from aminoglycosides (AGs) have been shown to exhibit enhanced antimicrobial activity. Through the attachment of hydrophobic residues such as linear alkyl chains on the AG backbone, interesting antibacterial and antifungal agents with a novel mechanism of action have been developed. Herein, we report the design and synthesis of seven kanamycin B (KANB) derivatives. Their antibacterial and antifungal activities, along with resistance/enzymatic, hemolytic, and cytotoxicity assays were also studied. Two of these compounds, with a C12 and C14 aliphatic chain attached at the 6″-position of KANB through a thioether linkage, exhibited good antibacterial and antifungal activity, were poorer substrates than KANB for several AG-modifying enzymes, and could delay the development of resistance in bacteria and fungi. Also, they were both relatively less hemolytic than the known membrane targeting antibiotic gramicidin and the known antifungal agent amphotericin B and were not toxic at their antifungal MIC values. Their oxidation to sulfones was also demonstrated to have no effect on their activities. Moreover, they both acted synergistically with posaconazole, an azole currently used in the treatment of human fungal infections.

Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Bacteria; Bacterial Infections; Cell Line; Cell Survival; Drug Design; Drug Resistance, Microbial; Fungi; Hemolysis; Humans; Kanamycin; Mice; Mycoses; Surface-Active Agents

Components of fatty acid biosynthetic pathway have been identified as attractive targets for the development of new antibacterial agents. Compounds of series A (4a-4 g) and series B (5a-5 g) were synthesized by the formation of an amine bond between aromatic acid and 4-phenylthiazol-2-amine or 4-(4-bromophenyl)thiazol-2-amine. These thiazole derivatives have evaluated as potent FabH inhibitors. Nineteen compounds (4b-4h, 4 k, 4 l, 5a-5h, 5k, 5l) are reported for the first time. Most of the synthesized compounds exhibited antibacterial activity in the MTT assay. The MIC value of these compounds ranged from 1.56 μg/mL to 100 μg/mL. Moreover, the tested compounds also showed FabH inhibition ability with IC50 value ranging from 5.8 μM to 48.1 μM. The IC50 values are near the MIC values. Compound 5f has exhibited the best antibacterial and Escherichia coli FabH inhibitory activity. Docking simulation and the QSAR study was conducted for learning about binding mode and the relationship between structure and activity.

Topics: 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; Acetyltransferases; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Design; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fatty Acid Synthase, Type II; Humans; Molecular Docking Simulation; Structure-Activity Relationship; Thiazoles

FabH, β-ketoacyl-acyl carrier protein (ACP) synthase III, is a particularly attractive target, since it is central to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and Gram-negative bacteria. A series of o-hydroxybenzylamines 1-16 and its corresponding new urea derivatives 17-32 were synthesized and fully characterized by spectroscopic methods and elemental analysis. This new urea derivatives class demonstrates strong antibacterial activity. Escherichia coli FabH inhibitory assay and docking simulation indicated that the compounds 1-(5-bromo-2-hydroxybenzyl)-1-(4-fluorophenyl)-3-phenylurea (18) and 1-(5-bromo-2-hydroxybenzyl)-1-(4-chlorophenyl)-3-phenylurea (20) were potent inhibitors of E. coli FabH.

Topics: 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Design; Enzyme Inhibitors; Escherichia coli; Escherichia coli Infections; Gram-Negative Bacteria; Humans; Microbial Sensitivity Tests; Models, Molecular; Protein Binding; Urea

The synthesis and biological properties of 1-N-[4-(substituted)amidino and guanidino-2-hydroxybutyryl]kanamycins A and B are described. Reaction of 3,3",6'-tri-N-tert-butoxycarbonyl-amikacin with an appropriate amidinating or guanidinating reagent and subsequent deblocking gave a series of amikacin derivatives having an amidino or guanidino group on the 4"'-position. The corresponding kanamycin B analogs were also prepared by a similar procedure. Among these derivatives, 1-N-(4-formamidino- and guanidino-2-hydroxybutyryl)kanamycins A (7a and 7k) and B (11 and 14) exhibited antibacterial activity similar to the corresponding 4-amino analogs. The nephrotoxic potential of selected compounds is also briefly discussed.

Topics: Animals; Bacteria; Bacterial Infections; Kanamycin; Kidney; Lethal Dose 50; Magnetic Resonance Spectroscopy; Mice; Molecular Structure

Topics: Adolescent; Adult; Aged; Bacterial Infections; Bronchiectasis; Bronchitis; Bronchopneumonia; Female; Humans; Kanamycin; Male; Middle Aged; Respiratory Tract Infections