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Sci Adv 2021 Mar 3;7(10). Epub 2021 Mar 3.

Laboratory of Molecular Pharmacology, Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

The widely used quinolone antibiotics act by trapping prokaryotic type IIA topoisomerases, resulting in irreversible topoisomerase cleavage complexes (TOPcc). Whereas the excision repair pathways of TOPcc in eukaryotes have been extensively studied, it is not known whether equivalent repair pathways for prokaryotic TOPcc exist. By combining genetic, biochemical, and molecular biology approaches, we demonstrate that exonuclease VII (ExoVII) excises quinolone-induced trapped DNA gyrase, an essential prokaryotic type IIA topoisomerase. Read More

Cell Rep 2021 Mar;34(9):108797

Department of Biochemistry, Light Hall, Vanderbilt University, Nashville, TN, USA. Electronic address:

Conflicts between the replication and transcription machineries have profound effects on chromosome duplication, genome organization, and evolution across species. Head-on conflicts (lagging-strand genes) are significantly more detrimental than codirectional conflicts (leading-strand genes). The fundamental reason for this difference is unknown. Read More

Arch Pharm (Weinheim) 2021 Mar 3:e2000473. Epub 2021 Mar 3.

Bioorganic and Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Prayagraj, Uttar Pradesh, India.

Bacterial infections are a serious threat to human health due to the development of resistance against the presently used antibiotics. The problem of growing and widespread antibiotic resistance is only getting worse with the shortage of new classes of antibiotics, creating a substantial unmet medical need in the treatment of serious bacterial infections. Therefore, in the present work, we report 18 novel hybrid thiazolidine-1,2,4-triazole derivatives as DNA gyrase inhibitors. Read More

Chem Biol Drug Des 2021 Feb 26. Epub 2021 Feb 26.

School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin University, Bentley Perth, WA, 6102, Australia.

Several rationally designed isoniazid (INH), pyrazinamide (PZA) and ciprofloxacin (CPF) derivatives were conveniently synthesised and evaluated in vitro against H37Rv M. tb strain. CPF derivative 16 displayed a modest activity (MIC = 16 µg/mL) and was docked into the M. Read More

Acc Chem Res 2021 Feb 26. Epub 2021 Feb 26.

Department of Chemistry Institute for Genomic Biology, University of Illinois, Urbana-Champaign, Urbana, Illinois 61801, United States.

ConspectusIt has been over half a century since the last class of antibiotics active against the most problematic Gram-negative bacteria was approved by the Food and Drug Administration (FDA). The major challenge with developing antibiotics to treat these infections is not drug-target engagement but rather the inability of most small molecules to traverse the Gram-negative membranes, be retained, and accumulate within the cell. Despite an abundance of lead compounds, limited understanding of the physicochemical properties needed for compound accumulation (or avoidance of efflux) in Gram-negative bacteria has precluded a generalizable approach for developing Gram-negative antibiotics. Read More