New chemotypes for wALADin1-like inhibitors of delta-aminolevulinic acid dehydratase from Wolbachia endobacteria
Substituted benzimidazoles of the wALADin1-family have recently been identified as a new class of species-selective inhibitors of delta-aminolevulinic acid dehydratase (ALAD) from Wolbachia endobacteria of parasitic filarial worms. Due to its Wolbachia-dependent antifilarial activity, wALADin1 is a...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2013-10, Vol.23 (20), p.5558-5562 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Lentz, Christian S. Stumpfe, Dagmar Bajorath, Juergen Famulok, Michael Hoerauf, Achim Pfarr, Kenneth M. |
| description | Substituted benzimidazoles of the wALADin1-family have recently been identified as a new class of species-selective inhibitors of delta-aminolevulinic acid dehydratase (ALAD) from Wolbachia endobacteria of parasitic filarial worms. Due to its Wolbachia-dependent antifilarial activity, wALADin1 is a starting point for the development of new drugs against filarial nematodes. We now present several other chemotypes of ALAD inhibitors that have been identified based upon their molecular similarity to wALADin1. A tricyclic quinoline derivative (wALADin2) with a different inhibitory mechanism and improved inhibitory potency and selectivity may represent an improved drug lead candidate. |
| doi_str_mv | 10.1016/j.bmcl.2013.08.052 |
| format | Article |
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Due to its Wolbachia-dependent antifilarial activity, wALADin1 is a starting point for the development of new drugs against filarial nematodes. We now present several other chemotypes of ALAD inhibitors that have been identified based upon their molecular similarity to wALADin1. A tricyclic quinoline derivative (wALADin2) with a different inhibitory mechanism and improved inhibitory potency and selectivity may represent an improved drug lead candidate.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2013.08.052</identifier><identifier>PMID: 24012123</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; benzimidazoles ; Benzimidazoles - chemical synthesis ; Benzimidazoles - chemistry ; Benzimidazoles - metabolism ; Brugia malayi ; Brugia malayi - enzymology ; chemistry ; chemotypes ; Delta-aminolevulinic acid dehydratase ; Enzyme Inhibitors - chemical synthesis ; Enzyme Inhibitors - chemistry ; Enzyme Inhibitors - metabolism ; Filaricides - chemical synthesis ; Filaricides - chemistry ; Filaricides - metabolism ; Heme biosynthesis ; Kinetics ; nematicides ; Nematoda ; new drugs ; Porphobilinogen Synthase - antagonists & inhibitors ; Porphobilinogen Synthase - metabolism ; Protein Binding ; quinoline ; Quinolines - chemistry ; Structure-Activity Relationship ; Thiophenes - chemical synthesis ; Thiophenes - chemistry ; Thiophenes - metabolism ; wALADin ; Wolbachia ; Wolbachia - enzymology</subject><ispartof>Bioorganic & medicinal chemistry letters, 2013-10, Vol.23 (20), p.5558-5562</ispartof><rights>2013 Elsevier Ltd</rights><rights>Copyright © 2013 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-43c777f3fad639e445ff39b1af73ec1be26a6109124ac05268f9f2394d8202ce3</citedby><cites>FETCH-LOGICAL-c413t-43c777f3fad639e445ff39b1af73ec1be26a6109124ac05268f9f2394d8202ce3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2013.08.052$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24012123$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lentz, Christian S.</creatorcontrib><creatorcontrib>Stumpfe, Dagmar</creatorcontrib><creatorcontrib>Bajorath, Juergen</creatorcontrib><creatorcontrib>Famulok, Michael</creatorcontrib><creatorcontrib>Hoerauf, Achim</creatorcontrib><creatorcontrib>Pfarr, Kenneth M.</creatorcontrib><title>New chemotypes for wALADin1-like inhibitors of delta-aminolevulinic acid dehydratase from Wolbachia endobacteria</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>Substituted benzimidazoles of the wALADin1-family have recently been identified as a new class of species-selective inhibitors of delta-aminolevulinic acid dehydratase (ALAD) from Wolbachia endobacteria of parasitic filarial worms. Due to its Wolbachia-dependent antifilarial activity, wALADin1 is a starting point for the development of new drugs against filarial nematodes. We now present several other chemotypes of ALAD inhibitors that have been identified based upon their molecular similarity to wALADin1. A tricyclic quinoline derivative (wALADin2) with a different inhibitory mechanism and improved inhibitory potency and selectivity may represent an improved drug lead candidate.</description><subject>Animals</subject><subject>benzimidazoles</subject><subject>Benzimidazoles - chemical synthesis</subject><subject>Benzimidazoles - chemistry</subject><subject>Benzimidazoles - metabolism</subject><subject>Brugia malayi</subject><subject>Brugia malayi - enzymology</subject><subject>chemistry</subject><subject>chemotypes</subject><subject>Delta-aminolevulinic acid dehydratase</subject><subject>Enzyme Inhibitors - chemical synthesis</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Enzyme Inhibitors - metabolism</subject><subject>Filaricides - chemical synthesis</subject><subject>Filaricides - chemistry</subject><subject>Filaricides - metabolism</subject><subject>Heme biosynthesis</subject><subject>Kinetics</subject><subject>nematicides</subject><subject>Nematoda</subject><subject>new drugs</subject><subject>Porphobilinogen Synthase - antagonists & inhibitors</subject><subject>Porphobilinogen Synthase - metabolism</subject><subject>Protein Binding</subject><subject>quinoline</subject><subject>Quinolines - chemistry</subject><subject>Structure-Activity Relationship</subject><subject>Thiophenes - chemical synthesis</subject><subject>Thiophenes - chemistry</subject><subject>Thiophenes - metabolism</subject><subject>wALADin</subject><subject>Wolbachia</subject><subject>Wolbachia - enzymology</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcuOEzEQRS0EYsLAD7AAL9l0U370S2ITDU8pggWMYGe57TJxcLczdmdG-XscZWAJqyqpTl3dqkvIcwY1A9a-3tXjZELNgYka-hoa_oCsmGxlJSQ0D8kKhhaqfpA_LsiTnHcATIKUj8kFl8A442JF9p_xjpotTnE57jFTFxO9W2_Wb_3MquB_IfXz1o9-iSnT6KjFsOhKT36OAW8Pwc_eUG28LZPt0Sa96IzUpTjR7zGM2my9pjjbWNoFk9dPySOnQ8Zn9_WSXL9_9-3qY7X58uHT1XpTGcnEUklhuq5zwmnbigGlbJwTw8i06wQaNiJvdctgYFxqUy5vezc4LgZpew7coLgkr866-xRvDpgXNflsMAQ9YzxkxRqArmm7Af6PyvJPBrLrCsrPqEkx54RO7ZOfdDoqBuoUitqpUyjqFIqCXhVrZenFvf5hnND-XfmTQgFengGno9I_k8_q-mtRKBaZ4LLvC_HmTGB52a3HpLLxOBu0PqFZlI3-Xw5-A0tIpxI</recordid><startdate>20131015</startdate><enddate>20131015</enddate><creator>Lentz, Christian S.</creator><creator>Stumpfe, Dagmar</creator><creator>Bajorath, Juergen</creator><creator>Famulok, Michael</creator><creator>Hoerauf, Achim</creator><creator>Pfarr, Kenneth M.</creator><general>Elsevier Ltd</general><scope>FBQ</scope><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>7X8</scope><scope>7QL</scope><scope>7QO</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20131015</creationdate><title>New chemotypes for wALADin1-like inhibitors of delta-aminolevulinic acid dehydratase from Wolbachia endobacteria</title><author>Lentz, Christian S. ; 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Due to its Wolbachia-dependent antifilarial activity, wALADin1 is a starting point for the development of new drugs against filarial nematodes. We now present several other chemotypes of ALAD inhibitors that have been identified based upon their molecular similarity to wALADin1. A tricyclic quinoline derivative (wALADin2) with a different inhibitory mechanism and improved inhibitory potency and selectivity may represent an improved drug lead candidate.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>24012123</pmid><doi>10.1016/j.bmcl.2013.08.052</doi><tpages>5</tpages></addata></record> |
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| subjects | Animals benzimidazoles Benzimidazoles - chemical synthesis Benzimidazoles - chemistry Benzimidazoles - metabolism Brugia malayi Brugia malayi - enzymology chemistry chemotypes Delta-aminolevulinic acid dehydratase Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Enzyme Inhibitors - metabolism Filaricides - chemical synthesis Filaricides - chemistry Filaricides - metabolism Heme biosynthesis Kinetics nematicides Nematoda new drugs Porphobilinogen Synthase - antagonists & inhibitors Porphobilinogen Synthase - metabolism Protein Binding quinoline Quinolines - chemistry Structure-Activity Relationship Thiophenes - chemical synthesis Thiophenes - chemistry Thiophenes - metabolism wALADin Wolbachia Wolbachia - enzymology |
| title | New chemotypes for wALADin1-like inhibitors of delta-aminolevulinic acid dehydratase from Wolbachia endobacteria |
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