New marine-derived indolymethyl pyrazinoquinazoline alkaloids with promising antimicrobial profiles
Due to the emergence of multidrug-resistant pathogenic microorganisms, the search for novel antimicrobials is urgent. Inspired by marine alkaloids, a series of indolomethyl pyrazino [1,2- b ]quinazoline-3,6-diones was prepared using a one-pot microwave-assisted multicomponent polycondensation of ami...
Gespeichert in:
| Veröffentlicht in: | RSC advances 2020-08, Vol.1 (52), p.31187-3124 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 3124 |
|---|---|
| container_issue | 52 |
| container_start_page | 31187 |
| container_title | RSC advances |
| container_volume | 1 |
| creator | Long, Solida Resende, Diana I. S. P Palmeira, Andreia Kijjoa, Anake Silva, Artur M. S Tiritan, Maria Elizabeth Pereira-Terra, Patrícia Freitas-Silva, Joana Barreiro, Sandra Silva, Renata Remião, Fernando Pinto, Eugénia Martins da Costa, Paulo Sousa, Emília Pinto, Madalena M. M |
| description | Due to the emergence of multidrug-resistant pathogenic microorganisms, the search for novel antimicrobials is urgent. Inspired by marine alkaloids, a series of indolomethyl pyrazino [1,2-
b
]quinazoline-3,6-diones was prepared using a one-pot microwave-assisted multicomponent polycondensation of amino acids. The compounds were evaluated for their antimicrobial activity against a panel of nine bacterial strains and five fungal strains. Compounds
26
and
27
were the most effective against
Staphylococcus aureus
ATCC 29213 reference strain with MIC values of 4 μg mL
−1
, and a methicillin-resistant
Staphylococcus aureus
(MRSA) isolate with MIC values of 8 μg mL
−1
. It was possible to infer that enantiomer (−)-
26
was responsible for the antibacterial activity (MIC 4 μg mL
−1
) while (+)-
26
had no activity. Furthermore, compound (−)-
26
was able to impair
S. aureus
biofilm production and no significant cytotoxicity towards differentiated and non-differentiated SH-SY5Y cells was observed. Compounds
26
,
28
, and
29
showed a weak antifungal activity against
Trichophyton rubrum
clinical isolate with MIC 128 μg mL
−1
and presented a synergistic effect with fluconazole.
Indolomethyl pyrazino [1,2-
b
]quinazoline-3,6-diones were prepared using a one-pot multicomponent polycondensation of amino acids and were evaluated for their antimicrobial activity against a panel of nine bacterial strains and five fungal strains. |
| doi_str_mv | 10.1039/d0ra05319h |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_rsc_p</sourceid><recordid>TN_cdi_proquest_miscellaneous_2661080929</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2661080929</sourcerecordid><originalsourceid>FETCH-LOGICAL-c454t-bc9f38a81cb7bc3f4a1ec76aa3d193fea921940a042fc95882c5bb7b34ec37b93</originalsourceid><addsrcrecordid>eNp9kc9LHDEUx0OxVLFevFemeCnC1PycnVyERVstSAXRc3iTybjRTDIms8r61zfr2q32YC4J-X54733fF6Fdgr8TzORhiyNgwYicfUBbFPOqpLiSG6_em2gnpVucTyUIrcgntMmEyArnW0j_No9FD9F6U7Ym2gfTFta3wS16M84WrhgWEZ6sD_dz6-EpuAwW4O7ABdum4tGOs2KIobfJ-psC_Gh7q2NoLLjlf2edSZ_Rxw5cMjsv9za6_vnj6visPL84_XU8PS81F3wsGy07VkNNdDNpNOs4EKMnFQBriWSdAUmJ5Bgwp52Woq6pFk1GGTeaTRrJttHRqu4wb3rTauPHCE4N0WaDCxXAqreKtzN1Ex6UxKJiNcsFvr0UiNmvSaPKvrRxDrwJ86RoVRFcY0mXvfb_Q2_DPPpsT1HOJnnBQpBMHayovJKUounWwxCslvGpE3w5fY7vLMN7r8dfo3_DysCXFRCTXqv_8s_61_d0NbQd-wM_o64y</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2437355551</pqid></control><display><type>article</type><title>New marine-derived indolymethyl pyrazinoquinazoline alkaloids with promising antimicrobial profiles</title><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><creator>Long, Solida ; Resende, Diana I. S. P ; Palmeira, Andreia ; Kijjoa, Anake ; Silva, Artur M. S ; Tiritan, Maria Elizabeth ; Pereira-Terra, Patrícia ; Freitas-Silva, Joana ; Barreiro, Sandra ; Silva, Renata ; Remião, Fernando ; Pinto, Eugénia ; Martins da Costa, Paulo ; Sousa, Emília ; Pinto, Madalena M. M</creator><creatorcontrib>Long, Solida ; Resende, Diana I. S. P ; Palmeira, Andreia ; Kijjoa, Anake ; Silva, Artur M. S ; Tiritan, Maria Elizabeth ; Pereira-Terra, Patrícia ; Freitas-Silva, Joana ; Barreiro, Sandra ; Silva, Renata ; Remião, Fernando ; Pinto, Eugénia ; Martins da Costa, Paulo ; Sousa, Emília ; Pinto, Madalena M. M</creatorcontrib><description>Due to the emergence of multidrug-resistant pathogenic microorganisms, the search for novel antimicrobials is urgent. Inspired by marine alkaloids, a series of indolomethyl pyrazino [1,2-
b
]quinazoline-3,6-diones was prepared using a one-pot microwave-assisted multicomponent polycondensation of amino acids. The compounds were evaluated for their antimicrobial activity against a panel of nine bacterial strains and five fungal strains. Compounds
26
and
27
were the most effective against
Staphylococcus aureus
ATCC 29213 reference strain with MIC values of 4 μg mL
−1
, and a methicillin-resistant
Staphylococcus aureus
(MRSA) isolate with MIC values of 8 μg mL
−1
. It was possible to infer that enantiomer (−)-
26
was responsible for the antibacterial activity (MIC 4 μg mL
−1
) while (+)-
26
had no activity. Furthermore, compound (−)-
26
was able to impair
S. aureus
biofilm production and no significant cytotoxicity towards differentiated and non-differentiated SH-SY5Y cells was observed. Compounds
26
,
28
, and
29
showed a weak antifungal activity against
Trichophyton rubrum
clinical isolate with MIC 128 μg mL
−1
and presented a synergistic effect with fluconazole.
Indolomethyl pyrazino [1,2-
b
]quinazoline-3,6-diones were prepared using a one-pot multicomponent polycondensation of amino acids and were evaluated for their antimicrobial activity against a panel of nine bacterial strains and five fungal strains.</description><identifier>ISSN: 2046-2069</identifier><identifier>EISSN: 2046-2069</identifier><identifier>DOI: 10.1039/d0ra05319h</identifier><identifier>PMID: 35520644</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Alkaloids ; Amino acids ; Antimicrobial agents ; Chemistry ; Diketones ; Enantiomers ; Fungicides ; Microorganisms ; Staphylococcus infections ; Synergistic effect ; Toxicity</subject><ispartof>RSC advances, 2020-08, Vol.1 (52), p.31187-3124</ispartof><rights>This journal is © The Royal Society of Chemistry.</rights><rights>Copyright Royal Society of Chemistry 2020</rights><rights>This journal is © The Royal Society of Chemistry 2020 The Royal Society of Chemistry</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-bc9f38a81cb7bc3f4a1ec76aa3d193fea921940a042fc95882c5bb7b34ec37b93</citedby><cites>FETCH-LOGICAL-c454t-bc9f38a81cb7bc3f4a1ec76aa3d193fea921940a042fc95882c5bb7b34ec37b93</cites><orcidid>0000-0002-3142-4864 ; 0000-0002-4077-6060 ; 0000-0002-4676-1409 ; 0000-0002-3321-1061 ; 0000-0001-6115-8811 ; 0000-0003-3320-730X ; 0000-0003-2455-1512 ; 0000-0003-1382-5119 ; 0000-0002-5397-4672 ; 0000-0003-2861-8286 ; 0000-0002-0235-4991 ; 0000-0002-1317-665X ; 0000-0001-9962-7548 ; 0000-0002-1391-2143 ; 0000-0003-2948-5809</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9056383/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9056383/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35520644$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Long, Solida</creatorcontrib><creatorcontrib>Resende, Diana I. S. P</creatorcontrib><creatorcontrib>Palmeira, Andreia</creatorcontrib><creatorcontrib>Kijjoa, Anake</creatorcontrib><creatorcontrib>Silva, Artur M. S</creatorcontrib><creatorcontrib>Tiritan, Maria Elizabeth</creatorcontrib><creatorcontrib>Pereira-Terra, Patrícia</creatorcontrib><creatorcontrib>Freitas-Silva, Joana</creatorcontrib><creatorcontrib>Barreiro, Sandra</creatorcontrib><creatorcontrib>Silva, Renata</creatorcontrib><creatorcontrib>Remião, Fernando</creatorcontrib><creatorcontrib>Pinto, Eugénia</creatorcontrib><creatorcontrib>Martins da Costa, Paulo</creatorcontrib><creatorcontrib>Sousa, Emília</creatorcontrib><creatorcontrib>Pinto, Madalena M. M</creatorcontrib><title>New marine-derived indolymethyl pyrazinoquinazoline alkaloids with promising antimicrobial profiles</title><title>RSC advances</title><addtitle>RSC Adv</addtitle><description>Due to the emergence of multidrug-resistant pathogenic microorganisms, the search for novel antimicrobials is urgent. Inspired by marine alkaloids, a series of indolomethyl pyrazino [1,2-
b
]quinazoline-3,6-diones was prepared using a one-pot microwave-assisted multicomponent polycondensation of amino acids. The compounds were evaluated for their antimicrobial activity against a panel of nine bacterial strains and five fungal strains. Compounds
26
and
27
were the most effective against
Staphylococcus aureus
ATCC 29213 reference strain with MIC values of 4 μg mL
−1
, and a methicillin-resistant
Staphylococcus aureus
(MRSA) isolate with MIC values of 8 μg mL
−1
. It was possible to infer that enantiomer (−)-
26
was responsible for the antibacterial activity (MIC 4 μg mL
−1
) while (+)-
26
had no activity. Furthermore, compound (−)-
26
was able to impair
S. aureus
biofilm production and no significant cytotoxicity towards differentiated and non-differentiated SH-SY5Y cells was observed. Compounds
26
,
28
, and
29
showed a weak antifungal activity against
Trichophyton rubrum
clinical isolate with MIC 128 μg mL
−1
and presented a synergistic effect with fluconazole.
Indolomethyl pyrazino [1,2-
b
]quinazoline-3,6-diones were prepared using a one-pot multicomponent polycondensation of amino acids and were evaluated for their antimicrobial activity against a panel of nine bacterial strains and five fungal strains.</description><subject>Alkaloids</subject><subject>Amino acids</subject><subject>Antimicrobial agents</subject><subject>Chemistry</subject><subject>Diketones</subject><subject>Enantiomers</subject><subject>Fungicides</subject><subject>Microorganisms</subject><subject>Staphylococcus infections</subject><subject>Synergistic effect</subject><subject>Toxicity</subject><issn>2046-2069</issn><issn>2046-2069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kc9LHDEUx0OxVLFevFemeCnC1PycnVyERVstSAXRc3iTybjRTDIms8r61zfr2q32YC4J-X54733fF6Fdgr8TzORhiyNgwYicfUBbFPOqpLiSG6_em2gnpVucTyUIrcgntMmEyArnW0j_No9FD9F6U7Ym2gfTFta3wS16M84WrhgWEZ6sD_dz6-EpuAwW4O7ABdum4tGOs2KIobfJ-psC_Gh7q2NoLLjlf2edSZ_Rxw5cMjsv9za6_vnj6visPL84_XU8PS81F3wsGy07VkNNdDNpNOs4EKMnFQBriWSdAUmJ5Bgwp52Woq6pFk1GGTeaTRrJttHRqu4wb3rTauPHCE4N0WaDCxXAqreKtzN1Ex6UxKJiNcsFvr0UiNmvSaPKvrRxDrwJ86RoVRFcY0mXvfb_Q2_DPPpsT1HOJnnBQpBMHayovJKUounWwxCslvGpE3w5fY7vLMN7r8dfo3_DysCXFRCTXqv_8s_61_d0NbQd-wM_o64y</recordid><startdate>20200821</startdate><enddate>20200821</enddate><creator>Long, Solida</creator><creator>Resende, Diana I. S. P</creator><creator>Palmeira, Andreia</creator><creator>Kijjoa, Anake</creator><creator>Silva, Artur M. S</creator><creator>Tiritan, Maria Elizabeth</creator><creator>Pereira-Terra, Patrícia</creator><creator>Freitas-Silva, Joana</creator><creator>Barreiro, Sandra</creator><creator>Silva, Renata</creator><creator>Remião, Fernando</creator><creator>Pinto, Eugénia</creator><creator>Martins da Costa, Paulo</creator><creator>Sousa, Emília</creator><creator>Pinto, Madalena M. M</creator><general>Royal Society of Chemistry</general><general>The Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3142-4864</orcidid><orcidid>https://orcid.org/0000-0002-4077-6060</orcidid><orcidid>https://orcid.org/0000-0002-4676-1409</orcidid><orcidid>https://orcid.org/0000-0002-3321-1061</orcidid><orcidid>https://orcid.org/0000-0001-6115-8811</orcidid><orcidid>https://orcid.org/0000-0003-3320-730X</orcidid><orcidid>https://orcid.org/0000-0003-2455-1512</orcidid><orcidid>https://orcid.org/0000-0003-1382-5119</orcidid><orcidid>https://orcid.org/0000-0002-5397-4672</orcidid><orcidid>https://orcid.org/0000-0003-2861-8286</orcidid><orcidid>https://orcid.org/0000-0002-0235-4991</orcidid><orcidid>https://orcid.org/0000-0002-1317-665X</orcidid><orcidid>https://orcid.org/0000-0001-9962-7548</orcidid><orcidid>https://orcid.org/0000-0002-1391-2143</orcidid><orcidid>https://orcid.org/0000-0003-2948-5809</orcidid></search><sort><creationdate>20200821</creationdate><title>New marine-derived indolymethyl pyrazinoquinazoline alkaloids with promising antimicrobial profiles</title><author>Long, Solida ; Resende, Diana I. S. P ; Palmeira, Andreia ; Kijjoa, Anake ; Silva, Artur M. S ; Tiritan, Maria Elizabeth ; Pereira-Terra, Patrícia ; Freitas-Silva, Joana ; Barreiro, Sandra ; Silva, Renata ; Remião, Fernando ; Pinto, Eugénia ; Martins da Costa, Paulo ; Sousa, Emília ; Pinto, Madalena M. M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-bc9f38a81cb7bc3f4a1ec76aa3d193fea921940a042fc95882c5bb7b34ec37b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alkaloids</topic><topic>Amino acids</topic><topic>Antimicrobial agents</topic><topic>Chemistry</topic><topic>Diketones</topic><topic>Enantiomers</topic><topic>Fungicides</topic><topic>Microorganisms</topic><topic>Staphylococcus infections</topic><topic>Synergistic effect</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Long, Solida</creatorcontrib><creatorcontrib>Resende, Diana I. S. P</creatorcontrib><creatorcontrib>Palmeira, Andreia</creatorcontrib><creatorcontrib>Kijjoa, Anake</creatorcontrib><creatorcontrib>Silva, Artur M. S</creatorcontrib><creatorcontrib>Tiritan, Maria Elizabeth</creatorcontrib><creatorcontrib>Pereira-Terra, Patrícia</creatorcontrib><creatorcontrib>Freitas-Silva, Joana</creatorcontrib><creatorcontrib>Barreiro, Sandra</creatorcontrib><creatorcontrib>Silva, Renata</creatorcontrib><creatorcontrib>Remião, Fernando</creatorcontrib><creatorcontrib>Pinto, Eugénia</creatorcontrib><creatorcontrib>Martins da Costa, Paulo</creatorcontrib><creatorcontrib>Sousa, Emília</creatorcontrib><creatorcontrib>Pinto, Madalena M. M</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>RSC advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Long, Solida</au><au>Resende, Diana I. S. P</au><au>Palmeira, Andreia</au><au>Kijjoa, Anake</au><au>Silva, Artur M. S</au><au>Tiritan, Maria Elizabeth</au><au>Pereira-Terra, Patrícia</au><au>Freitas-Silva, Joana</au><au>Barreiro, Sandra</au><au>Silva, Renata</au><au>Remião, Fernando</au><au>Pinto, Eugénia</au><au>Martins da Costa, Paulo</au><au>Sousa, Emília</au><au>Pinto, Madalena M. M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New marine-derived indolymethyl pyrazinoquinazoline alkaloids with promising antimicrobial profiles</atitle><jtitle>RSC advances</jtitle><addtitle>RSC Adv</addtitle><date>2020-08-21</date><risdate>2020</risdate><volume>1</volume><issue>52</issue><spage>31187</spage><epage>3124</epage><pages>31187-3124</pages><issn>2046-2069</issn><eissn>2046-2069</eissn><abstract>Due to the emergence of multidrug-resistant pathogenic microorganisms, the search for novel antimicrobials is urgent. Inspired by marine alkaloids, a series of indolomethyl pyrazino [1,2-
b
]quinazoline-3,6-diones was prepared using a one-pot microwave-assisted multicomponent polycondensation of amino acids. The compounds were evaluated for their antimicrobial activity against a panel of nine bacterial strains and five fungal strains. Compounds
26
and
27
were the most effective against
Staphylococcus aureus
ATCC 29213 reference strain with MIC values of 4 μg mL
−1
, and a methicillin-resistant
Staphylococcus aureus
(MRSA) isolate with MIC values of 8 μg mL
−1
. It was possible to infer that enantiomer (−)-
26
was responsible for the antibacterial activity (MIC 4 μg mL
−1
) while (+)-
26
had no activity. Furthermore, compound (−)-
26
was able to impair
S. aureus
biofilm production and no significant cytotoxicity towards differentiated and non-differentiated SH-SY5Y cells was observed. Compounds
26
,
28
, and
29
showed a weak antifungal activity against
Trichophyton rubrum
clinical isolate with MIC 128 μg mL
−1
and presented a synergistic effect with fluconazole.
Indolomethyl pyrazino [1,2-
b
]quinazoline-3,6-diones were prepared using a one-pot multicomponent polycondensation of amino acids and were evaluated for their antimicrobial activity against a panel of nine bacterial strains and five fungal strains.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>35520644</pmid><doi>10.1039/d0ra05319h</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0002-3142-4864</orcidid><orcidid>https://orcid.org/0000-0002-4077-6060</orcidid><orcidid>https://orcid.org/0000-0002-4676-1409</orcidid><orcidid>https://orcid.org/0000-0002-3321-1061</orcidid><orcidid>https://orcid.org/0000-0001-6115-8811</orcidid><orcidid>https://orcid.org/0000-0003-3320-730X</orcidid><orcidid>https://orcid.org/0000-0003-2455-1512</orcidid><orcidid>https://orcid.org/0000-0003-1382-5119</orcidid><orcidid>https://orcid.org/0000-0002-5397-4672</orcidid><orcidid>https://orcid.org/0000-0003-2861-8286</orcidid><orcidid>https://orcid.org/0000-0002-0235-4991</orcidid><orcidid>https://orcid.org/0000-0002-1317-665X</orcidid><orcidid>https://orcid.org/0000-0001-9962-7548</orcidid><orcidid>https://orcid.org/0000-0002-1391-2143</orcidid><orcidid>https://orcid.org/0000-0003-2948-5809</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2046-2069 |
| ispartof | RSC advances, 2020-08, Vol.1 (52), p.31187-3124 |
| issn | 2046-2069 2046-2069 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2661080929 |
| source | DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; PubMed Central Open Access |
| subjects | Alkaloids Amino acids Antimicrobial agents Chemistry Diketones Enantiomers Fungicides Microorganisms Staphylococcus infections Synergistic effect Toxicity |
| title | New marine-derived indolymethyl pyrazinoquinazoline alkaloids with promising antimicrobial profiles |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T14%3A42%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_rsc_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=New%20marine-derived%20indolymethyl%20pyrazinoquinazoline%20alkaloids%20with%20promising%20antimicrobial%20profiles&rft.jtitle=RSC%20advances&rft.au=Long,%20Solida&rft.date=2020-08-21&rft.volume=1&rft.issue=52&rft.spage=31187&rft.epage=3124&rft.pages=31187-3124&rft.issn=2046-2069&rft.eissn=2046-2069&rft_id=info:doi/10.1039/d0ra05319h&rft_dat=%3Cproquest_rsc_p%3E2661080929%3C/proquest_rsc_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2437355551&rft_id=info:pmid/35520644&rfr_iscdi=true |