Novel Penicillin-Based Sulfone-Siderophore Conjugates for Restoring β‑Lactam Antibiotic Efficacy
Membrane permeability is a natural defense barrier that contributes to increased bacterial drug resistance, particularly for Gram-negative pathogens. As such, accurate delivery of the antibacterial agent to the target has become a growing research area in the infectious diseases field as a means of...
Saved in:
| Published in | ACS omega Vol. 9; no. 24; pp. 26484 - 26494 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Chemical Society
18.06.2024
|
| Online Access | Get full text |
| ISSN | 2470-1343 2470-1343 |
| DOI | 10.1021/acsomega.4c02984 |
Cover
Loading…
| Abstract | Membrane permeability is a natural defense barrier that contributes to increased bacterial drug resistance, particularly for Gram-negative pathogens. As such, accurate delivery of the antibacterial agent to the target has become a growing research area in the infectious diseases field as a means of improving drug efficacy. Although the efficient transport of siderophore-antibiotic conjugates into the cytosol still remains challenging, great success has been achieved in the delivery of β-lactam antibiotics into the periplasmic space via bacterial iron uptake pathways. Cefiderocol, the first siderophore-cephalosporin conjugate approved by the US Food and Drug Administration, is a good example. These conjugation strategies have also been applied to the precise delivery of β-lactamase inhibitors, such as penicillin-based sulfone 1, to restore β-lactam antibiotic efficacy in multidrug-resistant bacteria. Herein, we have explored the impact on the bacterial activity of 1 by modifying its iron chelator moiety. A set of derivatives functionalized with diverse iron chelator groups and linkages to the scaffold (compounds 2–8) were synthesized and assayed in vitro. The results on the ability of derivatives 2–8 to recover β-lactam antibiotic efficacy in difficult-to-treat pathogens that produce various β-lactamase enzymes, along with kinetic studies with the isolated enzymes, allowed us to identify compound 2, a novel β-lactamase inhibitor with an expanded spectrum of activity. Molecular dynamics simulation studies provided us with further information regarding the molecular basis of the relative inhibitory properties of the most relevant compound described herein. |
|---|---|
| AbstractList | Membrane permeability is a natural defense barrier that
contributes
to increased bacterial drug resistance, particularly for Gram-negative
pathogens. As such, accurate delivery of the antibacterial agent to
the target has become a growing research area in the infectious diseases
field as a means of improving drug efficacy. Although the efficient
transport of siderophore-antibiotic conjugates into the cytosol still
remains challenging, great success has been achieved in the delivery
of β-lactam antibiotics into the periplasmic space via bacterial
iron uptake pathways. Cefiderocol, the first siderophore-cephalosporin
conjugate approved by the US Food and Drug Administration, is a good
example. These conjugation strategies have also been applied to the
precise delivery of β-lactamase inhibitors, such as penicillin-based
sulfone
1
, to restore β-lactam antibiotic efficacy
in multidrug-resistant bacteria. Herein, we have explored the impact
on the bacterial activity of
1
by modifying its iron
chelator moiety. A set of derivatives functionalized with diverse
iron chelator groups and linkages to the scaffold (compounds
2
–
8
) were synthesized and assayed in vitro.
The results on the ability of derivatives
2
–
8
to recover β-lactam antibiotic efficacy in difficult-to-treat
pathogens that produce various β-lactamase enzymes, along with
kinetic studies with the isolated enzymes, allowed us to identify
compound
2
, a novel β-lactamase inhibitor with
an expanded spectrum of activity. Molecular dynamics simulation studies
provided us with further information regarding the molecular basis
of the relative inhibitory properties of the most relevant compound
described herein. Membrane permeability is a natural defense barrier that contributes to increased bacterial drug resistance, particularly for Gram-negative pathogens. As such, accurate delivery of the antibacterial agent to the target has become a growing research area in the infectious diseases field as a means of improving drug efficacy. Although the efficient transport of siderophore-antibiotic conjugates into the cytosol still remains challenging, great success has been achieved in the delivery of β-lactam antibiotics into the periplasmic space via bacterial iron uptake pathways. Cefiderocol, the first siderophore-cephalosporin conjugate approved by the US Food and Drug Administration, is a good example. These conjugation strategies have also been applied to the precise delivery of β-lactamase inhibitors, such as penicillin-based sulfone 1, to restore β-lactam antibiotic efficacy in multidrug-resistant bacteria. Herein, we have explored the impact on the bacterial activity of 1 by modifying its iron chelator moiety. A set of derivatives functionalized with diverse iron chelator groups and linkages to the scaffold (compounds 2–8) were synthesized and assayed in vitro. The results on the ability of derivatives 2–8 to recover β-lactam antibiotic efficacy in difficult-to-treat pathogens that produce various β-lactamase enzymes, along with kinetic studies with the isolated enzymes, allowed us to identify compound 2, a novel β-lactamase inhibitor with an expanded spectrum of activity. Molecular dynamics simulation studies provided us with further information regarding the molecular basis of the relative inhibitory properties of the most relevant compound described herein. Membrane permeability is a natural defense barrier that contributes to increased bacterial drug resistance, particularly for Gram-negative pathogens. As such, accurate delivery of the antibacterial agent to the target has become a growing research area in the infectious diseases field as a means of improving drug efficacy. Although the efficient transport of siderophore-antibiotic conjugates into the cytosol still remains challenging, great success has been achieved in the delivery of β-lactam antibiotics into the periplasmic space via bacterial iron uptake pathways. Cefiderocol, the first siderophore-cephalosporin conjugate approved by the US Food and Drug Administration, is a good example. These conjugation strategies have also been applied to the precise delivery of β-lactamase inhibitors, such as penicillin-based sulfone , to restore β-lactam antibiotic efficacy in multidrug-resistant bacteria. Herein, we have explored the impact on the bacterial activity of by modifying its iron chelator moiety. A set of derivatives functionalized with diverse iron chelator groups and linkages to the scaffold (compounds - ) were synthesized and assayed in vitro. The results on the ability of derivatives - to recover β-lactam antibiotic efficacy in difficult-to-treat pathogens that produce various β-lactamase enzymes, along with kinetic studies with the isolated enzymes, allowed us to identify compound , a novel β-lactamase inhibitor with an expanded spectrum of activity. Molecular dynamics simulation studies provided us with further information regarding the molecular basis of the relative inhibitory properties of the most relevant compound described herein. Membrane permeability is a natural defense barrier that contributes to increased bacterial drug resistance, particularly for Gram-negative pathogens. As such, accurate delivery of the antibacterial agent to the target has become a growing research area in the infectious diseases field as a means of improving drug efficacy. Although the efficient transport of siderophore-antibiotic conjugates into the cytosol still remains challenging, great success has been achieved in the delivery of β-lactam antibiotics into the periplasmic space via bacterial iron uptake pathways. Cefiderocol, the first siderophore-cephalosporin conjugate approved by the US Food and Drug Administration, is a good example. These conjugation strategies have also been applied to the precise delivery of β-lactamase inhibitors, such as penicillin-based sulfone 1, to restore β-lactam antibiotic efficacy in multidrug-resistant bacteria. Herein, we have explored the impact on the bacterial activity of 1 by modifying its iron chelator moiety. A set of derivatives functionalized with diverse iron chelator groups and linkages to the scaffold (compounds 2-8) were synthesized and assayed in vitro. The results on the ability of derivatives 2-8 to recover β-lactam antibiotic efficacy in difficult-to-treat pathogens that produce various β-lactamase enzymes, along with kinetic studies with the isolated enzymes, allowed us to identify compound 2, a novel β-lactamase inhibitor with an expanded spectrum of activity. Molecular dynamics simulation studies provided us with further information regarding the molecular basis of the relative inhibitory properties of the most relevant compound described herein.Membrane permeability is a natural defense barrier that contributes to increased bacterial drug resistance, particularly for Gram-negative pathogens. As such, accurate delivery of the antibacterial agent to the target has become a growing research area in the infectious diseases field as a means of improving drug efficacy. Although the efficient transport of siderophore-antibiotic conjugates into the cytosol still remains challenging, great success has been achieved in the delivery of β-lactam antibiotics into the periplasmic space via bacterial iron uptake pathways. Cefiderocol, the first siderophore-cephalosporin conjugate approved by the US Food and Drug Administration, is a good example. These conjugation strategies have also been applied to the precise delivery of β-lactamase inhibitors, such as penicillin-based sulfone 1, to restore β-lactam antibiotic efficacy in multidrug-resistant bacteria. Herein, we have explored the impact on the bacterial activity of 1 by modifying its iron chelator moiety. A set of derivatives functionalized with diverse iron chelator groups and linkages to the scaffold (compounds 2-8) were synthesized and assayed in vitro. The results on the ability of derivatives 2-8 to recover β-lactam antibiotic efficacy in difficult-to-treat pathogens that produce various β-lactamase enzymes, along with kinetic studies with the isolated enzymes, allowed us to identify compound 2, a novel β-lactamase inhibitor with an expanded spectrum of activity. Molecular dynamics simulation studies provided us with further information regarding the molecular basis of the relative inhibitory properties of the most relevant compound described herein. |
| Author | Beceiro, Alejandro Vázquez-Ucha, Juan C. González-Bello, Concepción Rodríguez, Diana Lence, Emilio |
| AuthorAffiliation | Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Departamento de Química Orgánica Servicio de Microbiología, Complexo Hospitalario Universitario da Coruña (CHUAC) |
| AuthorAffiliation_xml | – name: Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Departamento de Química Orgánica – name: Servicio de Microbiología, Complexo Hospitalario Universitario da Coruña (CHUAC) |
| Author_xml | – sequence: 1 givenname: Diana surname: Rodríguez fullname: Rodríguez, Diana organization: Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Departamento de Química Orgánica – sequence: 2 givenname: Emilio orcidid: 0000-0001-9489-9421 surname: Lence fullname: Lence, Emilio organization: Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Departamento de Química Orgánica – sequence: 3 givenname: Juan C. surname: Vázquez-Ucha fullname: Vázquez-Ucha, Juan C. organization: Servicio de Microbiología, Complexo Hospitalario Universitario da Coruña (CHUAC) – sequence: 4 givenname: Alejandro orcidid: 0000-0002-6340-7815 surname: Beceiro fullname: Beceiro, Alejandro organization: Servicio de Microbiología, Complexo Hospitalario Universitario da Coruña (CHUAC) – sequence: 5 givenname: Concepción orcidid: 0000-0001-6439-553X surname: González-Bello fullname: González-Bello, Concepción email: concepcion.gonzalez.bello@usc.es organization: Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Departamento de Química Orgánica |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38911797$$D View this record in MEDLINE/PubMed |
| BookMark | eNp9ks9u1DAQxiNURP_QOyeUIwdSxk4cJyfUrgpUWgGicLZsZ5J65diLnVTqjVfgVfogPARPgsvuohYJTrY83_f7Rp45zPacd5hlzwicEKDkldTRjzjIk0oDbZvqUXZAKw4FKaty7959PzuOcQUApG5oQ-sn2X7ZtITwlh9k-r2_Rpt_RGe0sda44kxG7PLL2fYprrg0HQa_vvIB84V3q3mQE8a89yH_hHHywbgh_3H789v3pdSTHPNTNxll_GR0ft73Rkt98zR73Esb8Xh7HmVf3px_Xrwrlh_eXixOl4VkAFPBoFatZk1NkdGOIC-hajuiewpNxTTvNagSSgYd5z0gVaqtdc25VsCVqnh5lF1suJ2XK7EOZpThRnhpxO8HHwYhQ2rMooCmZoiMNFxjcqq26hhFRKVYD1zWifV6w1rPasROo5uCtA-gDyvOXInBXwtCSEugKRPhxZYQ_Nc5_ZUYTdRorXTo5yhK4ISRqqVtkj6_H_YnZTemJKg3Ah18jAF7oc0kJ-Pvso0VBMTdSojdSojtSiQj_GXcsf9jebmxpIpY-Tm4NLN_y38BvNjNHw |
| CitedBy_id | crossref_primary_10_1139_cjm_2024_0032 crossref_primary_10_1080_14787210_2024_2441891 crossref_primary_10_1002_cphc_202401057 |
| Cites_doi | 10.1007/s40265-021-01580-4 10.1021/acs.jmedchem.0c00127 10.1021/acsinfecdis.5b00007 10.1021/acsinfecdis.0c00798 10.1007/s40121-023-00773-6 10.1073/pnas.2305465120 10.1016/S1473-3099(20)30796-9 10.1093/cid/ciab757 10.1016/j.drudis.2023.103753 10.1021/acs.jmedchem.1c00369 10.1038/s41467-023-40828-3 10.1038/s41467-021-23191-z 10.1128/AAC.02171-20 10.1128/AAC.00592-18 10.1093/cid/ciz825 10.1016/j.ejmech.2022.114206 10.1021/acs.jmedchem.9b01279 10.1039/p19900000089 10.1111/1751-7915.12117 10.1038/s41579-019-0288-0 10.37201/req/s02.03.2022 10.1128/aac.01172-01117 10.1128/JCM.00951-20 10.1038/nbt.4193 10.1093/jac/dkw105 10.1021/acs.accounts.5b00301 10.1039/D2MD00465H 10.1016/S0040-4039(00)84819-4 10.2174/0929867043364847 10.1016/j.bmcl.2023.129282 10.1515/9783110527872-013 10.1006/jmbi.1996.0897 10.1021/ja104092z 10.1074/jbc.M806833200 10.1021/acsinfecdis.0c00568 10.1016/j.cbpa.2022.102160 10.1038/s41579-019-0284-4 10.1016/j.chembiol.2009.04.010 10.1128/aac.02247-12 |
| ContentType | Journal Article |
| Copyright | 2024 The Authors. Published by American Chemical Society 2024 The Authors. Published by American Chemical Society. 2024 The Authors. Published by American Chemical Society 2024 The Authors |
| Copyright_xml | – notice: 2024 The Authors. Published by American Chemical Society – notice: 2024 The Authors. Published by American Chemical Society. – notice: 2024 The Authors. Published by American Chemical Society 2024 The Authors |
| DBID | N~. AAYXX CITATION NPM 7X8 5PM DOA |
| DOI | 10.1021/acsomega.4c02984 |
| DatabaseName | American Chemical Society (ACS) Open Access CrossRef PubMed MEDLINE - Academic PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals |
| DatabaseTitle | CrossRef PubMed MEDLINE - Academic |
| DatabaseTitleList | PubMed MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: N~. name: American Chemical Society (ACS) Open Access url: https://pubs.acs.org sourceTypes: Publisher – sequence: 2 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 3 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Chemistry |
| EISSN | 2470-1343 |
| EndPage | 26494 |
| ExternalDocumentID | oai_doaj_org_article_0865ee5187ce473b94d52eeebb5f07a6 PMC11191083 38911797 10_1021_acsomega_4c02984 a338566501 |
| Genre | Journal Article |
| GroupedDBID | 53G AAFWJ AAHBH ABFRP ABUCX ACS ADBBV AFEFF AFPKN ALMA_UNASSIGNED_HOLDINGS AOIJS BCNDV EBS GROUPED_DOAJ HYE M~E N~. OK1 RPM VF5 AAYXX ABBLG ADUCK CITATION NPM 7X8 5PM |
| ID | FETCH-LOGICAL-a500t-506b9c5862e52d1e73049d1cf20845c7fc0b30350d77f0e2bb96c677cb07bb473 |
| IEDL.DBID | ACS |
| ISSN | 2470-1343 |
| IngestDate | Wed Aug 27 01:00:35 EDT 2025 Thu Aug 21 18:33:46 EDT 2025 Fri Jul 11 08:39:56 EDT 2025 Wed Feb 19 02:09:27 EST 2025 Tue Jul 01 00:50:09 EDT 2025 Thu Apr 24 23:03:36 EDT 2025 Tue Jun 25 16:50:41 EDT 2024 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 24 |
| Language | English |
| License | https://creativecommons.org/licenses/by-nc-nd/4.0 2024 The Authors. Published by American Chemical Society. Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-a500t-506b9c5862e52d1e73049d1cf20845c7fc0b30350d77f0e2bb96c677cb07bb473 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0001-6439-553X 0000-0002-6340-7815 0000-0001-9489-9421 |
| OpenAccessLink | https://proxy.k.utb.cz/login?url=http://dx.doi.org/10.1021/acsomega.4c02984 |
| PMID | 38911797 |
| PQID | 3071514929 |
| PQPubID | 23479 |
| PageCount | 11 |
| ParticipantIDs | doaj_primary_oai_doaj_org_article_0865ee5187ce473b94d52eeebb5f07a6 pubmedcentral_primary_oai_pubmedcentral_nih_gov_11191083 proquest_miscellaneous_3071514929 pubmed_primary_38911797 crossref_citationtrail_10_1021_acsomega_4c02984 crossref_primary_10_1021_acsomega_4c02984 acs_journals_10_1021_acsomega_4c02984 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2024-06-18 |
| PublicationDateYYYYMMDD | 2024-06-18 |
| PublicationDate_xml | – month: 06 year: 2024 text: 2024-06-18 day: 18 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | ACS omega |
| PublicationTitleAlternate | ACS Omega |
| PublicationYear | 2024 |
| Publisher | American Chemical Society |
| Publisher_xml | – name: American Chemical Society |
| References | ref9/cit9 ref6/cit6 ref36/cit36 ref3/cit3 ref27/cit27 CLSI (ref32/cit32) 2023 ref18/cit18 ref11/cit11 ref25/cit25 ref16/cit16 ref29/cit29 ref23/cit23 ref14/cit14 ref8/cit8 ref5/cit5 ref31/cit31 ref2/cit2 ref34/cit34 ref37/cit37 ref28/cit28 ref40/cit40 ref20/cit20 ref17/cit17 Case D. (ref39/cit39) 2021 ref10/cit10 ref26/cit26 ref35/cit35 ref19/cit19 ref21/cit21 ref12/cit12 ref15/cit15 ref42/cit42 ref41/cit41 ref22/cit22 ref13/cit13 ref33/cit33 ref4/cit4 ref30/cit30 ref1/cit1 ref24/cit24 ref38/cit38 DeLano W. L. (ref43/cit43) 2008 ref7/cit7 |
| References_xml | – ident: ref14/cit14 doi: 10.1007/s40265-021-01580-4 – ident: ref23/cit23 doi: 10.1021/acs.jmedchem.0c00127 – ident: ref37/cit37 doi: 10.1021/acsinfecdis.5b00007 – ident: ref41/cit41 doi: 10.1021/acsinfecdis.0c00798 – ident: ref18/cit18 doi: 10.1007/s40121-023-00773-6 – ident: ref3/cit3 doi: 10.1073/pnas.2305465120 – ident: ref12/cit12 doi: 10.1016/S1473-3099(20)30796-9 – ident: ref15/cit15 doi: 10.1093/cid/ciab757 – ident: ref1/cit1 doi: 10.1016/j.drudis.2023.103753 – ident: ref24/cit24 doi: 10.1021/acs.jmedchem.1c00369 – ident: ref19/cit19 doi: 10.1038/s41467-023-40828-3 – ident: ref27/cit27 doi: 10.1038/s41467-021-23191-z – ident: ref13/cit13 doi: 10.1128/AAC.02171-20 – ident: ref35/cit35 doi: 10.1128/AAC.00592-18 – ident: ref8/cit8 doi: 10.1093/cid/ciz825 – ident: ref22/cit22 – ident: ref42/cit42 doi: 10.1016/j.ejmech.2022.114206 – ident: ref6/cit6 doi: 10.1021/acs.jmedchem.9b01279 – ident: ref31/cit31 doi: 10.1039/p19900000089 – ident: ref29/cit29 doi: 10.1111/1751-7915.12117 – ident: ref4/cit4 doi: 10.1038/s41579-019-0288-0 – ident: ref17/cit17 doi: 10.37201/req/s02.03.2022 – ident: ref33/cit33 doi: 10.1128/aac.01172-01117 – volume-title: Performance Standards for Antimicrobial Susceptibility Testing year: 2023 ident: ref32/cit32 – ident: ref16/cit16 doi: 10.1128/JCM.00951-20 – ident: ref2/cit2 doi: 10.1038/nbt.4193 – ident: ref34/cit34 doi: 10.1093/jac/dkw105 – ident: ref30/cit30 doi: 10.1021/acs.accounts.5b00301 – ident: ref7/cit7 doi: 10.1039/D2MD00465H – ident: ref25/cit25 doi: 10.1016/S0040-4039(00)84819-4 – ident: ref20/cit20 doi: 10.2174/0929867043364847 – ident: ref9/cit9 doi: 10.1016/j.bmcl.2023.129282 – ident: ref11/cit11 doi: 10.1515/9783110527872-013 – ident: ref36/cit36 doi: 10.1006/jmbi.1996.0897 – ident: ref26/cit26 doi: 10.1021/ja104092z – ident: ref21/cit21 doi: 10.1074/jbc.M806833200 – ident: ref28/cit28 doi: 10.1021/acsinfecdis.0c00568 – ident: ref5/cit5 doi: 10.1016/j.cbpa.2022.102160 – volume-title: The PyMOL Molecular Graphics System year: 2008 ident: ref43/cit43 – volume-title: Amber 20 and AmberTools21 year: 2021 ident: ref39/cit39 – ident: ref10/cit10 doi: 10.1038/s41579-019-0284-4 – ident: ref40/cit40 doi: 10.1016/j.chembiol.2009.04.010 – ident: ref38/cit38 doi: 10.1128/aac.02247-12 |
| SSID | ssj0001682826 |
| Score | 2.2936227 |
| Snippet | Membrane permeability is a natural defense barrier that contributes to increased bacterial drug resistance, particularly for Gram-negative pathogens. As such,... Membrane permeability is a natural defense barrier that contributes to increased bacterial drug resistance, particularly for Gram-negative pathogens. As such,... |
| SourceID | doaj pubmedcentral proquest pubmed crossref acs |
| SourceType | Open Website Open Access Repository Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 26484 |
| SummonAdditionalLinks | – databaseName: DOAJ Directory of Open Access Journals dbid: DOA link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3NbtQwELZQL3BB_LNQkJHgwCFs4thxcmxXrSoEFaJU6i2yxxNatE2qZrcSN16BV-FBeAiehJn8rHYRKheuiS2PxmPPZ8_4GyFeKh9yYwNEWQZFpL1KI5c7jDD1NglJCBXy2-H3h9nBsX57Yk7WSn1xTlhPD9wrbkqQ2yCaJLeA2qa-0MEoRPTeVLF1Hdk2-by1w1R3u5LRSUKNcUnyY1MHbXOOn90bDcw6rtkbQbvhjTrS_r8hzT8TJtc80P4dcXuAjnKnF_muuIH1PXFzNlZsuy_gsLnCufyA9RnwNUod7ZKPCvJoOa-aGqMjfnLXXJw2lyhnTf1lyVdorSTYKj92BWbIjcmfP359-_7OwcKdy52aX5Q0NJ7cY6oJB18fiOP9vU-zg2goohBxrYNFZOLMF2Do4IJGhQQtx9VCApWKc23AVhD7lMOLwdoqRuV9kUFmLfjYek8afyi2apLxsZAVVlC4FGIMXvsq96lNbRECYaw80UZNxCtSaTksgrbs4tsqKUfVl4PqJ2I6Kr2EgYmcC2LMr-nxetXjomfhuKbtLs_jqh3zZ3cfyKrKwarKf1nVRLwYraCkSeQgiquxWbYl7YkEkjShyol41FvFaiiO-dIGZyci37CXDVk2_9Rnpx2nd8JEewSHn_wP6Z-KW4qwF2e0Jfm22FpcLvEZYaeFf94tk9-9Mh1I priority: 102 providerName: Directory of Open Access Journals |
| Title | Novel Penicillin-Based Sulfone-Siderophore Conjugates for Restoring β‑Lactam Antibiotic Efficacy |
| URI | http://dx.doi.org/10.1021/acsomega.4c02984 https://www.ncbi.nlm.nih.gov/pubmed/38911797 https://www.proquest.com/docview/3071514929 https://pubmed.ncbi.nlm.nih.gov/PMC11191083 https://doaj.org/article/0865ee5187ce473b94d52eeebb5f07a6 |
| Volume | 9 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3NbtQwELagHOBS_mn4qYwEBw7Zxo4dJ8ftaqsK0RViqdRb5J8JLWyTqkmQ4FDxCrwKD8JD8CSMs9ktW6qqFx8SO_HP2PN5xv6GkFfcuFQqZ8MksVkoDI9DnWoIITaKOeZcAf7u8N4k2d0Xbw_kwTlNzkUPPmdb2tbVMXzSA2E9Xbi4SW7xJFWeJ384mp7bUxLcO3TR1bhQUchiEfdeycs-4nWRrVd0UUfZfxnOvHhc8h_9s3N3Hsio7mgL_bGTL4O2MQP7_X9Sx2s07R5Z72EoHc7l5j65AeUDcnu0iP72kNhJ9RVm9D2UR9abZMpwG_Wdo9N2VlQlhFN_fa86OaxOgY6q8nPrzXE1RQhMP3TBalAl0t-__vz4-U7bRh_TYelvp1T4Pzr2tBXafntE9nfGH0e7YR-QIfRxE5pQRonJrMRNEEjuGCjvo3PMFjxKhbSqsJGJvavSKVVEwI3JEpsoZU2kjBEqfkzWSqzjBqEFFDbTsY3AGWGK1MQqVplziNdSJiQPyGvsnbyfUHXe-co5yxddlvddFpCtxRDmtmc198E1ZleUeLMscTJn9Lgi77aXimU-z8XdPcBRzPupneOmUAJIlioL2EaTCSc5ABgji0jpJCAvFzKV4yB6h4wuoWrrHNdXBFwCEWpAnsxlbPkr7z_GxVIFJF2RvpW6rL4pjw47fnDmSfsQWj-9Zh8-I3c4QjV_AI6lz8lac9rCC4Rajdns5thmZ6jAdO9sjOnkbPAXjaQsPA |
| linkProvider | American Chemical Society |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV3NbtQwELZKOZQL_z_h10hw4JBt7NhxctyuWi2wXaFuK_UWxfaEFrZJ1SRIcOIVeBUehIfgSRhnky1bVRVcnfhvPPZ89tjfEPKKaxtLZY0fRSbxheahn8UZ-BBqxSyzNgf3dnh3Go0PxLtDebhGWP8WBhtRYUlV68Q_Zxdgm5hWnsDHbCCMYw0X18h1xCLc0eUPR7PzY5UItxBtkDUuVOCzUISdc_KyQpxJMtWKSWqZ-y-DmxdvTf5lhnZukb1lB9rbJ58HTa0H5tsFbsf_6uFtcrMDpXS40KI7ZA2Ku2Rj1MeCu0fMtPwCc_oBimPjDmgKfwutn6WzZp6XBfgz95ivPD0qz4COyuJT4w7nKoqAmO61oWvQQNJfP39__zHJTJ2d0GHh3qqUWB_ddiQWmfl6nxzsbO-Pxn4XnsF3URRqXwaRTozELRFIbhko57GzzOQ8iIU0KjeBDp3j0iqVB8C1TiITKWV0oLQWKnxA1gts4yNCc8hNkoUmAKuFzmMdqlAl1iJ6i5mQ3COvUTppN72qtPWcc5b2Iks7kXlksx_J1HQc5y7UxvyKHG-WOU4X_B5X_LvllGP5n2PmbhNwJNNuoqe4RZQAksXKAPZRJ8JKDgBayzxQWeSRl71qpTiIzj2TFVA2VYqrLcIvgXjVIw8XqrasynmTcelUHolXlHClLatfiuOjli2cOQo_BNqP_1GGL8jGeH93kk7eTt8_ITc4gjh3NY7FT8l6fdbAMwRhtX7eTrs_v6oxXA |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV3NbtQwELZKkYAL_4XwGyQ4cMg2Tuw4OW6XrgqUVcVS1FsU2xNa2CarJkGCE6_Aq_AgPARPwkw2WdiqquDqxH_jseezx_6GsaeBtrFU1nhRZBJP6CD0sjgDD0KtuOXW5kBvh99Mop198epAHqwx2b-FwUZUWFLVOvFpVs9t3jEM8E1ML4_hQzYQhpjDxQV2kbx2RJk_HE3_HK1EuI1oA60FQvkeD0XYOSjPKoTMkqlWzFLL3n8W5Dx9c_IvUzS-xt4vO9HeQPk0aGo9MF9P8Tv-dy-vs6sdOHWHC226wdaguMkuj_qYcLeYmZSfYebuQXFk6KCm8LbQClp32szysgBvSo_6yvlheQLuqCw-NnRIV7kIjN23bQgbNJTuzx-_vn3fzUydHbvDgt6slFifu01kFpn5cpvtj7ffjXa8LkyDR9EUak_6kU6MxK0RyMByUOS5s9zkgR8LaVRufB2SA9MqlfsQaJ1EJlLKaF9pLVS4wdYLbONd5uaQmyQLjQ9WC53HOlShSqxFFBdzIQOHPUPppN00q9LWgx7wtBdZ2onMYZv9aKam4zqnkBuzc3I8X-aYL3g-zvl3ixRk-R8xdLcJOJppN-FT3CpKAMljZQD7qBNhZQAAWsvcV1nksCe9eqU4iOSmyQoomyrFVRdhmEDc6rA7C3VbVkVeZVxClcPiFUVcacvql-LosGUN50Tlh4D73j_K8DG7tPdinO6-nLy-z64EiOXohhyPH7D1-qSBh4jFav2onXm_AVqcM98 |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Novel+Penicillin-Based+Sulfone-Siderophore+Conjugates+for+Restoring+%CE%B2%E2%80%91Lactam+Antibiotic+Efficacy&rft.jtitle=ACS+omega&rft.au=Rodri%CC%81guez%2C+Diana&rft.au=Lence%2C+Emilio&rft.au=Va%CC%81zquez-Ucha%2C+Juan+C.&rft.au=Beceiro%2C+Alejandro&rft.date=2024-06-18&rft.pub=American+Chemical+Society&rft.issn=2470-1343&rft.eissn=2470-1343&rft.volume=9&rft.issue=24&rft.spage=26484&rft.epage=26494&rft_id=info:doi/10.1021%2Facsomega.4c02984&rft.externalDocID=a338566501 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2470-1343&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2470-1343&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2470-1343&client=summon |