FTR1335 Is a Novel Synthetic Inhibitor of Candida albicans N-Myristoyltransferase with Fungicidal Activity
Inhibitors of the fungal enzyme N-myristoyltransferase (Nmt) reduce fungal growth, as this enzyme is essential for viability. We found that a newly synthesized benzothiazole derivative, (1R,3S)-N-{2-[(cyclopeanthylcarbonyl) amino]-benzothiazol-6-yl}-3-[(2-naphthylmethyl) amino] cyclohexanecarboxamid...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 2005, Vol.28(4), pp.591-595 |
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| creator | Ebara, Shinji Naito, Hiroyuki Nakazawa, Kyoko Ishii, Fumio Nakamura, Masataka |
| description | Inhibitors of the fungal enzyme N-myristoyltransferase (Nmt) reduce fungal growth, as this enzyme is essential for viability. We found that a newly synthesized benzothiazole derivative, (1R,3S)-N-{2-[(cyclopeanthylcarbonyl) amino]-benzothiazol-6-yl}-3-[(2-naphthylmethyl) amino] cyclohexanecarboxamide (FTR1335), preferentially inhibited Candida albicans Nmt (CaNmt) in a dose-dependent manner. The 50% inhibitory concentration (IC50) for CaNmt was 0.49 nM, which was much lower than the 5400 nM IC50 for human Nmt (HsNmt1). The mode of CaNmt inhibition was competitive with the substrate peptide and non-competitive with myristoyl-CoA. Moreover, FTR1335 showed strong antifungal activity in vitro, and the minimum fungicidal concentration for C. albicans was 0.78 μM. These results indicate that FTR1335 might represent a novel family of Nmt inhibitors with fungicidal activity. |
| doi_str_mv | 10.1248/bpb.28.591 |
| format | Article |
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We found that a newly synthesized benzothiazole derivative, (1R,3S)-N-{2-[(cyclopeanthylcarbonyl) amino]-benzothiazol-6-yl}-3-[(2-naphthylmethyl) amino] cyclohexanecarboxamide (FTR1335), preferentially inhibited Candida albicans Nmt (CaNmt) in a dose-dependent manner. The 50% inhibitory concentration (IC50) for CaNmt was 0.49 nM, which was much lower than the 5400 nM IC50 for human Nmt (HsNmt1). The mode of CaNmt inhibition was competitive with the substrate peptide and non-competitive with myristoyl-CoA. Moreover, FTR1335 showed strong antifungal activity in vitro, and the minimum fungicidal concentration for C. albicans was 0.78 μM. These results indicate that FTR1335 might represent a novel family of Nmt inhibitors with fungicidal activity.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.28.591</identifier><identifier>PMID: 15802792</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>Acyltransferases - antagonists & inhibitors ; antifungal agent ; Antifungal Agents - chemistry ; Antifungal Agents - pharmacology ; Benzothiazoles ; Candida albicans ; Candida albicans - drug effects ; Candida albicans - enzymology ; Cyclohexanes - chemistry ; Cyclohexanes - pharmacology ; FTR1335 ; Molecular Structure ; N-myristoyltransferase (Nmt) ; Thiazoles - chemistry ; Thiazoles - pharmacology</subject><ispartof>Biological and Pharmaceutical Bulletin, 2005, Vol.28(4), pp.591-595</ispartof><rights>2005 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c502t-4e5a838c5b267d752634e9c3abe420751924706af06a11e7063f85529327a2ee3</citedby><cites>FETCH-LOGICAL-c502t-4e5a838c5b267d752634e9c3abe420751924706af06a11e7063f85529327a2ee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1883,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15802792$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ebara, Shinji</creatorcontrib><creatorcontrib>Naito, Hiroyuki</creatorcontrib><creatorcontrib>Nakazawa, Kyoko</creatorcontrib><creatorcontrib>Ishii, Fumio</creatorcontrib><creatorcontrib>Nakamura, Masataka</creatorcontrib><title>FTR1335 Is a Novel Synthetic Inhibitor of Candida albicans N-Myristoyltransferase with Fungicidal Activity</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>Inhibitors of the fungal enzyme N-myristoyltransferase (Nmt) reduce fungal growth, as this enzyme is essential for viability. We found that a newly synthesized benzothiazole derivative, (1R,3S)-N-{2-[(cyclopeanthylcarbonyl) amino]-benzothiazol-6-yl}-3-[(2-naphthylmethyl) amino] cyclohexanecarboxamide (FTR1335), preferentially inhibited Candida albicans Nmt (CaNmt) in a dose-dependent manner. The 50% inhibitory concentration (IC50) for CaNmt was 0.49 nM, which was much lower than the 5400 nM IC50 for human Nmt (HsNmt1). The mode of CaNmt inhibition was competitive with the substrate peptide and non-competitive with myristoyl-CoA. Moreover, FTR1335 showed strong antifungal activity in vitro, and the minimum fungicidal concentration for C. albicans was 0.78 μM. These results indicate that FTR1335 might represent a novel family of Nmt inhibitors with fungicidal activity.</description><subject>Acyltransferases - antagonists & inhibitors</subject><subject>antifungal agent</subject><subject>Antifungal Agents - chemistry</subject><subject>Antifungal Agents - pharmacology</subject><subject>Benzothiazoles</subject><subject>Candida albicans</subject><subject>Candida albicans - drug effects</subject><subject>Candida albicans - enzymology</subject><subject>Cyclohexanes - chemistry</subject><subject>Cyclohexanes - pharmacology</subject><subject>FTR1335</subject><subject>Molecular Structure</subject><subject>N-myristoyltransferase (Nmt)</subject><subject>Thiazoles - chemistry</subject><subject>Thiazoles - pharmacology</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1rGzEQhkVJaBy3l_6AIAjkUFhHnyvtKQQTp4YkhTY9C608G8usdx1Jm7L_vip2U8glCGnEzMMLw4PQF0pmlAl9We_qGdMzWdEPaEK5UIVkVB6hCamoLkoq9Qk6jXFDCFGE8Y_oJLcIUxWboM3i8QflXOJlxBY_9C_Q4p9jl9aQvMPLbu1rn_qA-wbPbbfyK4ttW3tnu4gfivsx-Jj6sU0hNxoINgL-7dMaL4buybuMt_jaJf_i0_gJHTe2jfD5UKfo1-Lmcf6tuPt-u5xf3xVOEpYKAdJqrp2sWalWSrKSC6gctzUIRpSkFROKlLbJl1LIX95oKVnFmbIMgE_RxT53F_rnAWIyWx8dtK3toB-iKZVUgjL9LkhVyTnJZ4rO34CbfghdXsJQISouqOBVpr7uKRf6GAM0Zhf81obRUGL-ijJZlGHaZFEZPjtEDvUWVv_Rg5kMXO2BTUz2CV4BG7KYFv5lif2TI18nbm2DgY7_Ab2bouk</recordid><startdate>20050401</startdate><enddate>20050401</enddate><creator>Ebara, Shinji</creator><creator>Naito, Hiroyuki</creator><creator>Nakazawa, Kyoko</creator><creator>Ishii, Fumio</creator><creator>Nakamura, Masataka</creator><general>The Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7T7</scope><scope>C1K</scope><scope>M7N</scope><scope>7X8</scope></search><sort><creationdate>20050401</creationdate><title>FTR1335 Is a Novel Synthetic Inhibitor of Candida albicans N-Myristoyltransferase with Fungicidal Activity</title><author>Ebara, Shinji ; Naito, Hiroyuki ; Nakazawa, Kyoko ; Ishii, Fumio ; Nakamura, Masataka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c502t-4e5a838c5b267d752634e9c3abe420751924706af06a11e7063f85529327a2ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Acyltransferases - antagonists & inhibitors</topic><topic>antifungal agent</topic><topic>Antifungal Agents - chemistry</topic><topic>Antifungal Agents - pharmacology</topic><topic>Benzothiazoles</topic><topic>Candida albicans</topic><topic>Candida albicans - drug effects</topic><topic>Candida albicans - enzymology</topic><topic>Cyclohexanes - chemistry</topic><topic>Cyclohexanes - pharmacology</topic><topic>FTR1335</topic><topic>Molecular Structure</topic><topic>N-myristoyltransferase (Nmt)</topic><topic>Thiazoles - chemistry</topic><topic>Thiazoles - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ebara, Shinji</creatorcontrib><creatorcontrib>Naito, Hiroyuki</creatorcontrib><creatorcontrib>Nakazawa, Kyoko</creatorcontrib><creatorcontrib>Ishii, Fumio</creatorcontrib><creatorcontrib>Nakamura, Masataka</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ebara, Shinji</au><au>Naito, Hiroyuki</au><au>Nakazawa, Kyoko</au><au>Ishii, Fumio</au><au>Nakamura, Masataka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FTR1335 Is a Novel Synthetic Inhibitor of Candida albicans N-Myristoyltransferase with Fungicidal Activity</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>2005-04-01</date><risdate>2005</risdate><volume>28</volume><issue>4</issue><spage>591</spage><epage>595</epage><pages>591-595</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>Inhibitors of the fungal enzyme N-myristoyltransferase (Nmt) reduce fungal growth, as this enzyme is essential for viability. We found that a newly synthesized benzothiazole derivative, (1R,3S)-N-{2-[(cyclopeanthylcarbonyl) amino]-benzothiazol-6-yl}-3-[(2-naphthylmethyl) amino] cyclohexanecarboxamide (FTR1335), preferentially inhibited Candida albicans Nmt (CaNmt) in a dose-dependent manner. The 50% inhibitory concentration (IC50) for CaNmt was 0.49 nM, which was much lower than the 5400 nM IC50 for human Nmt (HsNmt1). The mode of CaNmt inhibition was competitive with the substrate peptide and non-competitive with myristoyl-CoA. Moreover, FTR1335 showed strong antifungal activity in vitro, and the minimum fungicidal concentration for C. albicans was 0.78 μM. These results indicate that FTR1335 might represent a novel family of Nmt inhibitors with fungicidal activity.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>15802792</pmid><doi>10.1248/bpb.28.591</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | J-STAGE Free; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Free Full-Text Journals in Chemistry |
| subjects | Acyltransferases - antagonists & inhibitors antifungal agent Antifungal Agents - chemistry Antifungal Agents - pharmacology Benzothiazoles Candida albicans Candida albicans - drug effects Candida albicans - enzymology Cyclohexanes - chemistry Cyclohexanes - pharmacology FTR1335 Molecular Structure N-myristoyltransferase (Nmt) Thiazoles - chemistry Thiazoles - pharmacology |
| title | FTR1335 Is a Novel Synthetic Inhibitor of Candida albicans N-Myristoyltransferase with Fungicidal Activity |
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