title: Anti-methicillin resistant Staphylococcus aureus activity, synergism with oxacillin and molecular docking studies of metronidazole-triazole hybrids.
abstract: MRSA causes 60-70% of Staphylococcus aureus infection in hospitals and it has developed resistance against the currently available drugs. Interestingly, a series of 35 metronidazole-triazole hybrids on screening against MRSA were found to be active. Compound 22 was found to be effective at 4 μg/mL concentration against nine strains of MRSA. The inhibitory activity was further enhanced upto 1 μg/mL when this compound was used in combination with oxacillin in 1:1 ratio. All the compounds were found to be non-toxic in THP-1 cell line upto a concentration of 50 μM. The time-kill kinetics studies suggested bacteriostatic nature of the compounds. In silico studies show that these compounds interact with Thr600, Ser598, Asn464, His583 and Tyr446 in the active site of PBP2a crystal structure from MRSA.
authors.affiliation: Department of Chemistry, University of Delhi, Delhi 110007, India.
authors.forename: Beena
authors.initials: B
authors.lastname: Negi
authors.affiliation: Department of Chemistry, University of Delhi, Delhi 110007, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Mihinthale, Sri Lanka.
authors.forename: Widuranga
authors.initials: W
authors.lastname: Kumbukgolla
authors.affiliation: Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Mihinthale, Sri Lanka.
authors.forename: Sampath
authors.initials: S
authors.lastname: Jayaweera
authors.affiliation: Department of Chemistry, University of Delhi, Delhi 110007, India.
authors.forename: Prija
authors.initials: P
authors.lastname: Ponnan
authors.affiliation: Translational Health Science and Technology Institute, Vaccine and Infectious Disaease Research Centre, Gurgaon 122016, India.
authors.forename: Ramandeep
authors.initials: R
authors.lastname: Singh
authors.affiliation: Translational Health Science and Technology Institute, Vaccine and Infectious Disaease Research Centre, Gurgaon 122016, India.
authors.forename: Sakshi
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: Department of Chemistry, University of Delhi, Delhi 110007, India. Electronic address: dsrawat@chemistry.du.ac.in.
authors.forename: Diwan S
authors.initials: DS
authors.lastname: Rawat
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015169:Colony Count, Microbial; D004357:Drug Synergism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008795:Metronidazole / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014230:Triazoles; D008795:Metronidazole
keywords: MRSA; Methicillin; Metronidazole; Oxacillin; PBP2a; Triazole