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Repository of Research and Investigative Information

Hormozgan University of Medical Sciences

Identification of novel bacterial DNA gyrase inhibitors: An in silico study

(2016) Identification of novel bacterial DNA gyrase inhibitors: An in silico study. Research in Pharmaceutical Sciences.

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Abstract

Owing to essential role in bacterial survival, DNA gyrase has been exploited as a validated drug target. However, rapidly emerging resistance to gyrase-targeted drugs such as widely utilized fluoroquinolones reveals the necessity to develop novel compounds with new mechanism of actions against this enzyme. Here, an attempt has been made to identify new drug-like molecules for Shigella flexneri DNA gyrase inhibition through in silico approaches. The structural similarity search was carried out using the natural product simocyclinone D8, a unique gyrase inhibitor, to virtually screen ZINC database. A total of 11830 retrieved hits were further screened for selection of high-affinity compounds by implementing molecular docking followed by investigation of druggability according to Lipinski's rule, biological activity and physiochemical properties. Among the hits initially identified, three molecules were then confirmed to have reasonable gyrase-binding affinity and to follow Lipinski's rule. Based on these in silico findings, three compounds with different chemical structures from previously identified gyrase inhibitors were proposed as potential candidates for the treatment of fluoroquinolone-resistant strains and deserve further investigations.

Item Type: Article
Additional Information: cited By 1
Keywords: DNA topoisomerase (ATP hydrolysing); gyrase inhibitor; simocyclinone D8; unclassified drug; zinc 03952456; zinc 28243125; zinc 28530355; zinc 29590257; zinc 31425392; zinc 42802964; zinc 43335590; zinc 49654831; zinc 49813778; zinc 67829151; zinc 72185765; zinc 72186671; zinc 85506909; zinc 85509032; zinc 85531085; zinc 85531741; zinc 85593824; zinc 85594529; zinc 85628568; zinc 86039680, Article; binding affinity; computer model; drug protein binding; drug structure; enzyme inhibition; molecular docking; nonhuman; physical chemistry; Shigella flexneri; structural homology
Subjects: QU Biochemistry. Cell Biology and Genetics > QU 300-560 Cell Biology and Genetics
Divisions: Education Vice-Chancellor Department > Faculty of Pharmacy > Department of Pharmacognosy
Research Vice-Chancellor Department > Mother and Child Welfare Research Center
Depositing User: مهندس هدی فهیم پور
URI: http://eprints.hums.ac.ir/id/eprint/4147

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