A temperature sensitive mutant affecting the B-subunit of DNA gyrase was isolated. The mutation leads to the thermolability of DNA gyrase in vitro and to the plasmid DNA relaxation in vitro. The immediate stop of the increase in mutant culture titre has been observed under nonpermissive conditions. However, DNA synthesis does not cease, though its efficiency is reduced by a factor of three. The transcription rate is also reduced two - three times, but more quickly than the rate of replication. This would mean that the transcription apparatus is the first to react to the change of DNA supercoiling in the cell. This suggestion is supported by the facts that small amounts of rifampicin increase the viability of ts mutant cells under nonpermissive conditions and also by the previously obtained results concerning the change in sensitivity of RNA polymerase mutants to DNA gyrase inhibitors.
Download full-text PDF |
Source |
---|
Bioorg Chem
January 2025
Chemistry Department, Faculty of Science, Ain Shams University, Abbasia, 11566 Cairo, Egypt.
The escalating prevalence of antibiotic-resistant bacteria has led to a serious global public health problem; therefore, there is an urgent need for the development of structurally innovative antibacterial agents. In our study, different series of tetra-substituted thiophene derivatives were designed and synthesized by multi-component reactions (MCRs) in moderate to excellent yields. Some of the designed final compounds were synthesized by both microwave assisted method and traditional synthesis.
View Article and Find Full Text PDFRSC Adv
January 2025
Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Centre Dokki Giza 12622 Egypt
A novel molecular design based on a quinazolinone scaffold was developed the attachment of aryl alkanesulfonates to the quinazolinone core through a thioacetohydrazide azomethine linker, leading to a new series of quinazolinone-alkanesulfonates 5a-r. The antimicrobial properties of the newly synthesized quinazolinone derivatives 5a-r were investigated to examine their bactericidal and fungicidal activities against bacterial pathogens like , (Gram-positive), , , (Gram-negative), in addition to (unicellular fungal). The tested compounds demonstrated reasonable bactericidal activities compared to standard drugs.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Oscillation of the active form of the initiator protein DnaA (ATP-DnaA) allows for the timely regulation for chromosome replication. After initiation, DnaA-bound ATP is hydrolyzed, producing inactive ADP-DnaA. For the next round of initiation, ADP-DnaA interacts with the chromosomal locus DARS2 bearing binding sites for DnaA, a DNA-bending protein IHF, and a transcription activator Fis.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Medicines Discovery Institute, Cardiff University, Cardiff CF10 3AT, UK.
DNA gyrase is a bacterial type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology and an archetypical target of antibiotics. The widely used quinolone class of drugs use a water-metal ion bridge in interacting with the GyrA subunit of DNA gyrase. Zoliflodacin sits in the same pocket as quinolones but interacts with the GyrB subunit and also stabilizes lethal double-stranded DNA breaks.
View Article and Find Full Text PDFMolecules
December 2024
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, 90128 Palermo, Italy.
Molecular hybridization, which consists of the combination of two or more pharmacophores into a single molecule, is an innovative approach in drug design to afford new chemical entities with enhanced biological activity. In the present study, this strategy was pursued to develop a new series of 6,7-dimethoxy-4-piperazinylquinoline-3-carbonitrile derivatives (-) with potential antibiotic activity by combining the quinoline, the piperazinyl, and the benzoylamino moieties, three recurrent frameworks in antimicrobial research. Initial in silico evaluations were conducted on the designed compounds, highlighting favorable ADMET and drug-likeness properties, which were synthesized through a multistep strategy, isolated, and fully characterized.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!