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l-Ornithine-N5-monooxygenase (PvdA) Substrate Analogue Inhibitors for Pseudomonas aeruginosa Infections Treatment: Drug Repurposing Computational Studies

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cris.lastimport.scopus2024-02-12T19:57:26Z
dc.abstract.enPseudomonas aeruginosa is an opportunistic pathogen that can cause acute and severe infections. Increasing resistance to antibiotics has given rise to the urgent need for an alternative antimicrobial agent. A promising strategy is the inhibition of iron sequestration in the bacteria. The current work aimed to screen for inhibitors of pyoverdine-mediated iron sequestration in P. aeruginosa. As a drug target, we choose L-ornithine-N5-monooxygenase (PvdA), an enzyme involved in the biosynthesis of pyoverdine that catalyzes the FAD-dependent hydroxylation of the side chain amine of ornithine. As drug repurposing is a fast and cost-efficient way of discovering new applications for known drugs, the approach may help to solve emerging clinical problems. In this study, we use data about molecules from drug banks for screening. A total of 15 drugs that are similar in structure to L-ornithine, the substrate of PvdA, and 30 drugs that are sub-structures of L-ornithine were virtually docked against PvdA. N-2-succinyl ornithine and cilazapril were found to be the top binders with a binding energy of -12.8 and -9.1 kcal mol(-1), respectively. As the drug-likeness and ADME properties of the drugs were also found to be promising, molecular dynamics studies were performed to further confirm the stability of the complexes. The results of this in silico study indicate that N-2-succinyl ornithine could potentially be explored as a drug for the treatment of P. aeruginosa infections.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorBabkiewicz, Ewa
dc.contributor.authorMaszczyk, Piotr
dc.contributor.authorSundar, Krishnan
dc.contributor.authorKunjiappan, Selvaraj
dc.contributor.authorMurugesan, Sankaranarayanan
dc.contributor.authorKumar, Banoth Karan
dc.contributor.authorMrówka, Piotr
dc.contributor.authorRosy, Joseph Christina
dc.date.accessioned2024-01-25T05:24:43Z
dc.date.available2024-01-25T05:24:43Z
dc.date.copyright2022-06-25
dc.date.issued2022
dc.description.accesstimeAT_PUBLICATION
dc.description.financeNie dotyczy
dc.description.number7
dc.description.versionFINAL_PUBLISHED
dc.description.volume12
dc.identifier.doi10.3390/BIOM12070887
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/111528
dc.identifier.weblinkhttps://www.mdpi.com/2218-273X/12/7/887/pdf
dc.languageeng
dc.pbn.affiliationbiological sciences
dc.relation.ispartofBiomolecules
dc.relation.pages887
dc.rightsCC-BY
dc.sciencecloudnosend
dc.titlel-Ornithine-N5-monooxygenase (PvdA) Substrate Analogue Inhibitors for Pseudomonas aeruginosa Infections Treatment: Drug Repurposing Computational Studies
dc.typeJournalArticle
dspace.entity.typePublication