title: Design and Biological Evaluation of Furan/Pyrrole/Thiophene-2-carboxamide Derivatives as Efficient DNA GyraseB Inhibitors of Staphylococcus aureus.
abstract: DNA topoisomerases are well-validated targets in micro-organisms. DNA gyraseB is one of the most important enzymes among them as per their clinical importance. In earlier study, a novel lead 4-((4-(furan-2-carboxamido)phenyl)amino)-4-oxobutanoic acid was identified as inhibitor against DNA gyraseB with an IC50 of 12.88 ± 1.39 μm. Subsequently, analogues of this lead were developed and evaluated through in vitro assays and in vivo studies. Among the 24 analogues, compound 22 was found to be the top hit with an improved DNA gyraseB activity of 5.35 ± 0.61 μm, and the binding affinity of this compound was further ascertained biophysically through differential scanning fluorimetry. The most potent ligand did not show any signs of cardiotoxicity in zebra fish ether-ago-go-related gene, ascertaining the safety profile of this series a breakthrough among the previously reported cardiotoxic gyraseB inhibitors.
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Shameerpet, Jawahar Nagar, Ranga Reddy District, Hyderabad, 500078, Andhra Pradesh, India.
authors.forename: Renuka
authors.initials: R
authors.lastname: Janupally
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Shameerpet, Jawahar Nagar, Ranga Reddy District, Hyderabad, 500078, Andhra Pradesh, India.
authors.forename: Bhramam
authors.initials: B
authors.lastname: Medepi
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Shameerpet, Jawahar Nagar, Ranga Reddy District, Hyderabad, 500078, Andhra Pradesh, India.
authors.forename: Parthiban
authors.initials: P
authors.lastname: Brindha Devi
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Shameerpet, Jawahar Nagar, Ranga Reddy District, Hyderabad, 500078, Andhra Pradesh, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Suryadevara
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Shameerpet, Jawahar Nagar, Ranga Reddy District, Hyderabad, 500078, Andhra Pradesh, India.
authors.forename: Variam Ullas
authors.initials: VU
authors.lastname: Jeankumar
authors.affiliation: Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, 500046, Andhra Pradesh, India.|Zephase Therapeutics (An Incubated Company at the Dr. Reddy's Institute of Life Sciences), University of Hyderabad Campus, Gachibowli, Hyderabad, 500046, Andhra Pradesh, India.
authors.forename: Pushkar
authors.initials: P
authors.lastname: Kulkarni
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Shameerpet, Jawahar Nagar, Ranga Reddy District, Hyderabad, 500078, Andhra Pradesh, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Shameerpet, Jawahar Nagar, Ranga Reddy District, Hyderabad, 500078, Andhra Pradesh, India.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
mesh_terms: D000818:Animals; D027081:DNA Gyrase / Q000378:metabolism*; D005663:Furans / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D008958:Models, Molecular; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology*; D013876:Thiophenes / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D059005:Topoisomerase II Inhibitors / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D015027:Zebrafish
chemical_list: D005663:Furans; D011758:Pyrroles; D013876:Thiophenes; D059005:Topoisomerase II Inhibitors; D027081:DNA Gyrase
keywords: DNA gyrase; Staphylococcus aureus; biofilm; cytotoxicity