Selective Anti-Leishmanial Strathclyde Minor Groove Binders Using an N-Oxide Tail-Group Modification
The neglected tropical disease leishmaniasis, caused by Leishmania spp., is becoming more problematic due to the emergence of drug-resistant strains. Therefore, new drugs to treat leishmaniasis, with novel mechanisms of action, are urgently required. Strathclyde minor groove binders (S-MGBs) are an...
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| Veröffentlicht in: | International journal of molecular sciences 2022-10, Vol.23 (19), p.11912 |
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| creator | Perieteanu, Marina C McGee, Leah M C Shaw, Craig D MacMillan, Donna S Khalaf, Abedawn I Gillingwater, Kirsten Beveridge, Rebecca Carter, Katharine C Suckling, Colin J Scott, Fraser J |
| description | The neglected tropical disease leishmaniasis, caused by Leishmania spp., is becoming more problematic due to the emergence of drug-resistant strains. Therefore, new drugs to treat leishmaniasis, with novel mechanisms of action, are urgently required. Strathclyde minor groove binders (S-MGBs) are an emerging class of anti-infective agent that have been shown to have potent activity against various bacteria, viruses, fungi and parasites. Herein, it is shown that S-MGBs have potent activity against
, and that an N-oxide derivation of the tertiary amine tail of typical S-MGBs leads to selective anti-leishmanial activity. Additionally, using S-MGB-219, the N-oxide derivation is shown to retain strong binding to DNA as a 2:1 dimer. These findings support the further study of anti-leishmanial S-MGBs as novel therapeutics. |
| doi_str_mv | 10.3390/ijms231911912 |
| format | Article |
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, and that an N-oxide derivation of the tertiary amine tail of typical S-MGBs leads to selective anti-leishmanial activity. Additionally, using S-MGB-219, the N-oxide derivation is shown to retain strong binding to DNA as a 2:1 dimer. These findings support the further study of anti-leishmanial S-MGBs as novel therapeutics.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms231911912</identifier><identifier>PMID: 36233213</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Amines ; Antiinfectives and antibacterials ; Bacteria ; Derivation ; DNA - metabolism ; Drug resistance ; Gram-positive bacteria ; Grooves ; Hydrogenation ; Infections ; Leishmania - metabolism ; Leishmaniasis ; Oxides ; Parasites ; Parasitic diseases ; Public health ; Tropical diseases</subject><ispartof>International journal of molecular sciences, 2022-10, Vol.23 (19), p.11912</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-fc9021bd3426f4402143c9786722d50a9985d5e2bc5f2e93c56a59a6893a742b3</citedby><cites>FETCH-LOGICAL-c415t-fc9021bd3426f4402143c9786722d50a9985d5e2bc5f2e93c56a59a6893a742b3</cites><orcidid>0000-0001-9162-7527 ; 0000-0003-2507-1844 ; 0000-0003-0229-3698</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/PMC9569768/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569768/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36233213$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Perieteanu, Marina C</creatorcontrib><creatorcontrib>McGee, Leah M C</creatorcontrib><creatorcontrib>Shaw, Craig D</creatorcontrib><creatorcontrib>MacMillan, Donna S</creatorcontrib><creatorcontrib>Khalaf, Abedawn I</creatorcontrib><creatorcontrib>Gillingwater, Kirsten</creatorcontrib><creatorcontrib>Beveridge, Rebecca</creatorcontrib><creatorcontrib>Carter, Katharine C</creatorcontrib><creatorcontrib>Suckling, Colin J</creatorcontrib><creatorcontrib>Scott, Fraser J</creatorcontrib><title>Selective Anti-Leishmanial Strathclyde Minor Groove Binders Using an N-Oxide Tail-Group Modification</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>The neglected tropical disease leishmaniasis, caused by Leishmania spp., is becoming more problematic due to the emergence of drug-resistant strains. Therefore, new drugs to treat leishmaniasis, with novel mechanisms of action, are urgently required. Strathclyde minor groove binders (S-MGBs) are an emerging class of anti-infective agent that have been shown to have potent activity against various bacteria, viruses, fungi and parasites. Herein, it is shown that S-MGBs have potent activity against
, and that an N-oxide derivation of the tertiary amine tail of typical S-MGBs leads to selective anti-leishmanial activity. Additionally, using S-MGB-219, the N-oxide derivation is shown to retain strong binding to DNA as a 2:1 dimer. These findings support the further study of anti-leishmanial S-MGBs as novel therapeutics.</description><subject>Amines</subject><subject>Antiinfectives and antibacterials</subject><subject>Bacteria</subject><subject>Derivation</subject><subject>DNA - metabolism</subject><subject>Drug resistance</subject><subject>Gram-positive bacteria</subject><subject>Grooves</subject><subject>Hydrogenation</subject><subject>Infections</subject><subject>Leishmania - metabolism</subject><subject>Leishmaniasis</subject><subject>Oxides</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Public health</subject><subject>Tropical diseases</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkcFLHDEUxoNU1K49epWBXnqZmrxMMpNLQaXdFnb1oJ5DNpNx3zKTbJMZ6f73zaIVLTx4D96Pj-_jI-SM0a-cK3qBmyEBZ4rlgQNywiqAklJZf3hzH5OPKW0oBQ5CHZFjLoFzYPyEtHeud3bEJ1dc-hHLhcO0HoxH0xd3YzTj2va71hVL9CEW8xhCJq_Qty6m4iGhfyyML27K2z-YqXuDfZmhaVssQ4sdWjNi8KfksDN9cp9e9ow8_Ph-f_2zXNzOf11fLkpbMTGWnVUU2KrlFciuqvJdcavqRtYAraBGqUa0wsHKig6c4lZII5SRjeKmrmDFZ-Tbs-52Wg2utc7nBL3eRhxM3OlgUL__eFzrx_CklZCqlk0W-PIiEMPvyaVRD5is63vjXZiShhoEU9mQzOjn_9BNmKLP8fZUBappYE-Vz5SNIaXoulczjOp9f_pdf5k_f5vglf5XGP8L1wWWVw</recordid><startdate>20221007</startdate><enddate>20221007</enddate><creator>Perieteanu, Marina C</creator><creator>McGee, Leah M C</creator><creator>Shaw, Craig D</creator><creator>MacMillan, Donna S</creator><creator>Khalaf, Abedawn I</creator><creator>Gillingwater, Kirsten</creator><creator>Beveridge, Rebecca</creator><creator>Carter, Katharine C</creator><creator>Suckling, Colin J</creator><creator>Scott, Fraser J</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>COVID</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9162-7527</orcidid><orcidid>https://orcid.org/0000-0003-2507-1844</orcidid><orcidid>https://orcid.org/0000-0003-0229-3698</orcidid></search><sort><creationdate>20221007</creationdate><title>Selective Anti-Leishmanial Strathclyde Minor Groove Binders Using an N-Oxide Tail-Group Modification</title><author>Perieteanu, Marina C ; 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Therefore, new drugs to treat leishmaniasis, with novel mechanisms of action, are urgently required. Strathclyde minor groove binders (S-MGBs) are an emerging class of anti-infective agent that have been shown to have potent activity against various bacteria, viruses, fungi and parasites. Herein, it is shown that S-MGBs have potent activity against
, and that an N-oxide derivation of the tertiary amine tail of typical S-MGBs leads to selective anti-leishmanial activity. Additionally, using S-MGB-219, the N-oxide derivation is shown to retain strong binding to DNA as a 2:1 dimer. These findings support the further study of anti-leishmanial S-MGBs as novel therapeutics.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36233213</pmid><doi>10.3390/ijms231911912</doi><orcidid>https://orcid.org/0000-0001-9162-7527</orcidid><orcidid>https://orcid.org/0000-0003-2507-1844</orcidid><orcidid>https://orcid.org/0000-0003-0229-3698</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Amines Antiinfectives and antibacterials Bacteria Derivation DNA - metabolism Drug resistance Gram-positive bacteria Grooves Hydrogenation Infections Leishmania - metabolism Leishmaniasis Oxides Parasites Parasitic diseases Public health Tropical diseases |
| title | Selective Anti-Leishmanial Strathclyde Minor Groove Binders Using an N-Oxide Tail-Group Modification |
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