RapamycinFungusV1, Main, Exploration, bibRecord, 000483

Synthesis and anticancer activity of novel rapamycin C-28 containing triazole moiety compounds.

Identifieur interne : 000483 ( Main/Exploration ); précédent : 000482; suivant : 000484

Synthesis and anticancer activity of novel rapamycin C-28 containing triazole moiety compounds.

Auteurs : Qingwen Huang [République populaire de Chine] ; Lijun Xie [République populaire de Chine] ; Xiaoming Chen [République populaire de Chine] ; Hui Yu [République populaire de Chine] ; Yubing Lv [République populaire de Chine] ; Xuehui Huang [République populaire de Chine] ; Jiayin Ying [République populaire de Chine] ; Congshen Zheng [République populaire de Chine] ; Yuanrong Cheng [République populaire de Chine] ; Jie Huang [République populaire de Chine]

Source :

Archiv der Pharmazie [ 1521-4184 ] ; 2018.

RBID : pubmed:30357890

Descripteurs français

KwdFr :
- Antinéoplasiques (composition chimique), Antinéoplasiques (pharmacologie), Antinéoplasiques (synthèse chimique), Apoptose (effets des médicaments et des substances chimiques), Cellules cancéreuses en culture (MeSH), Humains (MeSH), Inhibiteurs de protéines kinases (composition chimique), Inhibiteurs de protéines kinases (pharmacologie), Inhibiteurs de protéines kinases (synthèse chimique), Phosphorylation (effets des médicaments et des substances chimiques), Points de contrôle du cycle cellulaire (effets des médicaments et des substances chimiques), Prolifération cellulaire (effets des médicaments et des substances chimiques), Relation dose-effet des médicaments (MeSH), Relation structure-activité (MeSH), Sirolimus (composition chimique), Sirolimus (pharmacologie), Sirolimus (synthèse chimique), Structure moléculaire (MeSH), Sérine-thréonine kinases TOR (antagonistes et inhibiteurs), Sérine-thréonine kinases TOR (métabolisme), Tests de criblage d'agents antitumoraux (MeSH), Transduction du signal (effets des médicaments et des substances chimiques), Triazoles (composition chimique), Triazoles (pharmacologie).
MESH :
- antagonistes et inhibiteurs : Sérine-thréonine kinases TOR.
- composition chimique : Antinéoplasiques, Inhibiteurs de protéines kinases, Sirolimus, Triazoles.
- effets des médicaments et des substances chimiques : Apoptose, Phosphorylation, Points de contrôle du cycle cellulaire, Prolifération cellulaire, Transduction du signal.
- métabolisme : Sérine-thréonine kinases TOR.
- pharmacologie : Antinéoplasiques, Inhibiteurs de protéines kinases, Sirolimus, Triazoles.
- synthèse chimique : Antinéoplasiques, Inhibiteurs de protéines kinases, Sirolimus.
- Cellules cancéreuses en culture, Humains, Relation dose-effet des médicaments, Relation structure-activité, Structure moléculaire, Tests de criblage d'agents antitumoraux.

English descriptors

KwdEn :
- Antineoplastic Agents (chemical synthesis), Antineoplastic Agents (chemistry), Antineoplastic Agents (pharmacology), Apoptosis (drug effects), Cell Cycle Checkpoints (drug effects), Cell Proliferation (drug effects), Dose-Response Relationship, Drug (MeSH), Drug Screening Assays, Antitumor (MeSH), Humans (MeSH), Molecular Structure (MeSH), Phosphorylation (drug effects), Protein Kinase Inhibitors (chemical synthesis), Protein Kinase Inhibitors (chemistry), Protein Kinase Inhibitors (pharmacology), Signal Transduction (drug effects), Sirolimus (chemical synthesis), Sirolimus (chemistry), Sirolimus (pharmacology), Structure-Activity Relationship (MeSH), TOR Serine-Threonine Kinases (antagonists & inhibitors), TOR Serine-Threonine Kinases (metabolism), Triazoles (chemistry), Triazoles (pharmacology), Tumor Cells, Cultured (MeSH).
MESH :
- chemical , antagonists & inhibitors : TOR Serine-Threonine Kinases.
- chemical , chemical synthesis : Antineoplastic Agents, Protein Kinase Inhibitors, Sirolimus.
- chemical , chemistry : Antineoplastic Agents, Protein Kinase Inhibitors, Sirolimus, Triazoles.
- chemical , metabolism : TOR Serine-Threonine Kinases.
- chemical , pharmacology : Antineoplastic Agents, Protein Kinase Inhibitors, Sirolimus, Triazoles.
- drug effects : Apoptosis, Cell Cycle Checkpoints, Cell Proliferation, Phosphorylation, Signal Transduction.
- Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Molecular Structure, Structure-Activity Relationship, Tumor Cells, Cultured.

Abstract

Rapamycin is an mTOR allosteric inhibitor with multiple functions such as immunosuppressive, anticancer, and lifespan prolonging activities. Its C-43 semi-synthetic derivatives temsirolimus and everolimus have been used as mTOR targeting anticancer drugs in the clinic. Following our previous research on antitumor rapalogs modified on the C-43 position, 13 novel rapamycin triazole hybrids (6a-g, 7a-f) were designed and synthesized on the C-28 position of rapamycin via Huisgen's reaction. Anticancer assays indicated that the targeted derivatives containing phenyl and 4-methylphenyl groups showed an obvious raise in anticancer activity. On the contrary, the compounds with methoxyl, amine, and halogen groups on the benzene ring displayed lower anticancer activity. Compound 6c, as the most active compound, showed a stronger inhibition effect as compared with rapamycin for almost all of the tested cell lines (p < 0.01), except PC-3. Meanwhile, the effect of 6c on inducing apoptosis and cell cycle arrest in A549 cells was more powerful than that of rapamycin. In addition, 6c inhibited the phosphorylation of mTOR and its downstream key kinases 4EBP1 and p70S6K1 in A549 cells, indicating that 6c also effectively inhibits the mTORC1 signaling pathway as rapamycin. On the basis of these findings, 6c may have the potential to be developed as a new mTOR inhibitor against specific cancers.

DOI: 10.1002/ardp.201800123
PubMed: 30357890

Affiliations:

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000421
to stream Main, to step Curation: 000421

Le document en format XML

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<author><name sortKey="Ying, Jiayin" sort="Ying, Jiayin" uniqKey="Ying J" first="Jiayin" last="Ying">Jiayin Ying</name>
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<author><name sortKey="Zheng, Congshen" sort="Zheng, Congshen" uniqKey="Zheng C" first="Congshen" last="Zheng">Congshen Zheng</name>
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<author><name sortKey="Cheng, Yuanrong" sort="Cheng, Yuanrong" uniqKey="Cheng Y" first="Yuanrong" last="Cheng">Yuanrong Cheng</name>
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<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
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<author><name sortKey="Huang, Jie" sort="Huang, Jie" uniqKey="Huang J" first="Jie" last="Huang">Jie Huang</name>
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<term>Antineoplastic Agents (chemistry)</term>
<term>Antineoplastic Agents (pharmacology)</term>
<term>Apoptosis (drug effects)</term>
<term>Cell Cycle Checkpoints (drug effects)</term>
<term>Cell Proliferation (drug effects)</term>
<term>Dose-Response Relationship, Drug (MeSH)</term>
<term>Drug Screening Assays, Antitumor (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Molecular Structure (MeSH)</term>
<term>Phosphorylation (drug effects)</term>
<term>Protein Kinase Inhibitors (chemical synthesis)</term>
<term>Protein Kinase Inhibitors (chemistry)</term>
<term>Protein Kinase Inhibitors (pharmacology)</term>
<term>Signal Transduction (drug effects)</term>
<term>Sirolimus (chemical synthesis)</term>
<term>Sirolimus (chemistry)</term>
<term>Sirolimus (pharmacology)</term>
<term>Structure-Activity Relationship (MeSH)</term>
<term>TOR Serine-Threonine Kinases (antagonists & inhibitors)</term>
<term>TOR Serine-Threonine Kinases (metabolism)</term>
<term>Triazoles (chemistry)</term>
<term>Triazoles (pharmacology)</term>
<term>Tumor Cells, Cultured (MeSH)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Antinéoplasiques (composition chimique)</term>
<term>Antinéoplasiques (pharmacologie)</term>
<term>Antinéoplasiques (synthèse chimique)</term>
<term>Apoptose (effets des médicaments et des substances chimiques)</term>
<term>Cellules cancéreuses en culture (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Inhibiteurs de protéines kinases (composition chimique)</term>
<term>Inhibiteurs de protéines kinases (pharmacologie)</term>
<term>Inhibiteurs de protéines kinases (synthèse chimique)</term>
<term>Phosphorylation (effets des médicaments et des substances chimiques)</term>
<term>Points de contrôle du cycle cellulaire (effets des médicaments et des substances chimiques)</term>
<term>Prolifération cellulaire (effets des médicaments et des substances chimiques)</term>
<term>Relation dose-effet des médicaments (MeSH)</term>
<term>Relation structure-activité (MeSH)</term>
<term>Sirolimus (composition chimique)</term>
<term>Sirolimus (pharmacologie)</term>
<term>Sirolimus (synthèse chimique)</term>
<term>Structure moléculaire (MeSH)</term>
<term>Sérine-thréonine kinases TOR (antagonistes et inhibiteurs)</term>
<term>Sérine-thréonine kinases TOR (métabolisme)</term>
<term>Tests de criblage d'agents antitumoraux (MeSH)</term>
<term>Transduction du signal (effets des médicaments et des substances chimiques)</term>
<term>Triazoles (composition chimique)</term>
<term>Triazoles (pharmacologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Antineoplastic Agents</term>
<term>Protein Kinase Inhibitors</term>
<term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antineoplastic Agents</term>
<term>Protein Kinase Inhibitors</term>
<term>Sirolimus</term>
<term>Triazoles</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Agents</term>
<term>Protein Kinase Inhibitors</term>
<term>Sirolimus</term>
<term>Triazoles</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>Antinéoplasiques</term>
<term>Inhibiteurs de protéines kinases</term>
<term>Sirolimus</term>
<term>Triazoles</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term>
<term>Cell Cycle Checkpoints</term>
<term>Cell Proliferation</term>
<term>Phosphorylation</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Apoptose</term>
<term>Phosphorylation</term>
<term>Points de contrôle du cycle cellulaire</term>
<term>Prolifération cellulaire</term>
<term>Transduction du signal</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antinéoplasiques</term>
<term>Inhibiteurs de protéines kinases</term>
<term>Sirolimus</term>
<term>Triazoles</term>
</keywords>
<keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Antinéoplasiques</term>
<term>Inhibiteurs de protéines kinases</term>
<term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Dose-Response Relationship, Drug</term>
<term>Drug Screening Assays, Antitumor</term>
<term>Humans</term>
<term>Molecular Structure</term>
<term>Structure-Activity Relationship</term>
<term>Tumor Cells, Cultured</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Cellules cancéreuses en culture</term>
<term>Humains</term>
<term>Relation dose-effet des médicaments</term>
<term>Relation structure-activité</term>
<term>Structure moléculaire</term>
<term>Tests de criblage d'agents antitumoraux</term>
</keywords>
</textClass>
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<front><div type="abstract" xml:lang="en">Rapamycin is an mTOR allosteric inhibitor with multiple functions such as immunosuppressive, anticancer, and lifespan prolonging activities. Its C-43 semi-synthetic derivatives temsirolimus and everolimus have been used as mTOR targeting anticancer drugs in the clinic. Following our previous research on antitumor rapalogs modified on the C-43 position, 13 novel rapamycin triazole hybrids (6a-g, 7a-f) were designed and synthesized on the C-28 position of rapamycin via Huisgen's reaction. Anticancer assays indicated that the targeted derivatives containing phenyl and 4-methylphenyl groups showed an obvious raise in anticancer activity. On the contrary, the compounds with methoxyl, amine, and halogen groups on the benzene ring displayed lower anticancer activity. Compound 6c, as the most active compound, showed a stronger inhibition effect as compared with rapamycin for almost all of the tested cell lines (p < 0.01), except PC-3. Meanwhile, the effect of 6c on inducing apoptosis and cell cycle arrest in A549 cells was more powerful than that of rapamycin. In addition, 6c inhibited the phosphorylation of mTOR and its downstream key kinases 4EBP1 and p70S6K1 in A549 cells, indicating that 6c also effectively inhibits the mTORC1 signaling pathway as rapamycin. On the basis of these findings, 6c may have the potential to be developed as a new mTOR inhibitor against specific cancers.</div>
</front>
</TEI>
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<DateCompleted><Year>2019</Year>
<Month>04</Month>
<Day>08</Day>
</DateCompleted>
<DateRevised><Year>2019</Year>
<Month>04</Month>
<Day>08</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1521-4184</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>351</Volume>
<Issue>11</Issue>
<PubDate><Year>2018</Year>
<Month>Nov</Month>
</PubDate>
</JournalIssue>
<Title>Archiv der Pharmazie</Title>
<ISOAbbreviation>Arch Pharm (Weinheim)</ISOAbbreviation>
</Journal>
<ArticleTitle>Synthesis and anticancer activity of novel rapamycin C-28 containing triazole moiety compounds.</ArticleTitle>
<Pagination><MedlinePgn>e1800123</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1002/ardp.201800123</ELocationID>
<Abstract><AbstractText>Rapamycin is an mTOR allosteric inhibitor with multiple functions such as immunosuppressive, anticancer, and lifespan prolonging activities. Its C-43 semi-synthetic derivatives temsirolimus and everolimus have been used as mTOR targeting anticancer drugs in the clinic. Following our previous research on antitumor rapalogs modified on the C-43 position, 13 novel rapamycin triazole hybrids (6a-g, 7a-f) were designed and synthesized on the C-28 position of rapamycin via Huisgen's reaction. Anticancer assays indicated that the targeted derivatives containing phenyl and 4-methylphenyl groups showed an obvious raise in anticancer activity. On the contrary, the compounds with methoxyl, amine, and halogen groups on the benzene ring displayed lower anticancer activity. Compound 6c, as the most active compound, showed a stronger inhibition effect as compared with rapamycin for almost all of the tested cell lines (p < 0.01), except PC-3. Meanwhile, the effect of 6c on inducing apoptosis and cell cycle arrest in A549 cells was more powerful than that of rapamycin. In addition, 6c inhibited the phosphorylation of mTOR and its downstream key kinases 4EBP1 and p70S6K1 in A549 cells, indicating that 6c also effectively inhibits the mTORC1 signaling pathway as rapamycin. On the basis of these findings, 6c may have the potential to be developed as a new mTOR inhibitor against specific cancers.</AbstractText>
<CopyrightInformation>© 2018 Deutsche Pharmazeutische Gesellschaft.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Huang</LastName>
<ForeName>Qingwen</ForeName>
<Initials>Q</Initials>
<Identifier Source="ORCID">https://orcid.org/0000-0001-8999-1215</Identifier>
<AffiliationInfo><Affiliation>Fujian University of Traditional Chinese Medicine, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Xie</LastName>
<ForeName>Lijun</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chen</LastName>
<ForeName>Xiaoming</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yu</LastName>
<ForeName>Hui</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lv</LastName>
<ForeName>Yubing</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Hangzhou Huadong Medicine Group Pharmaceutical Research Institute Co. Ltd., Hangzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Huang</LastName>
<ForeName>XueHui</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Hangzhou Huadong Medicine Group Pharmaceutical Research Institute Co. Ltd., Hangzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ying</LastName>
<ForeName>Jiayin</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zheng</LastName>
<ForeName>Congshen</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cheng</LastName>
<ForeName>Yuanrong</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Huang</LastName>
<ForeName>Jie</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Fujian University of Traditional Chinese Medicine, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, P. R. China.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>81502935</GrantID>
<Agency>National Natural Science Foundation of China</Agency>
<Country></Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2018</Year>
<Month>10</Month>
<Day>25</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>Germany</Country>
<MedlineTA>Arch Pharm (Weinheim)</MedlineTA>
<NlmUniqueID>0330167</NlmUniqueID>
<ISSNLinking>0365-6233</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000970">Antineoplastic Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D047428">Protein Kinase Inhibitors</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014230">Triazoles</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
<NameOfSubstance UI="C546842">MTOR protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
<NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>W36ZG6FT64</RegistryNumber>
<NameOfSubstance UI="D020123">Sirolimus</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000970" MajorTopicYN="N">Antineoplastic Agents</DescriptorName>
<QualifierName UI="Q000138" MajorTopicYN="N">chemical synthesis</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D017209" MajorTopicYN="N">Apoptosis</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D059447" MajorTopicYN="N">Cell Cycle Checkpoints</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004354" MajorTopicYN="N">Drug Screening Assays, Antitumor</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015394" MajorTopicYN="N">Molecular Structure</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D010766" MajorTopicYN="N">Phosphorylation</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D047428" MajorTopicYN="N">Protein Kinase Inhibitors</DescriptorName>
<QualifierName UI="Q000138" MajorTopicYN="N">chemical synthesis</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D020123" MajorTopicYN="N">Sirolimus</DescriptorName>
<QualifierName UI="Q000138" MajorTopicYN="N">chemical synthesis</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013329" MajorTopicYN="N">Structure-Activity Relationship</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014230" MajorTopicYN="N">Triazoles</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014407" MajorTopicYN="N">Tumor Cells, Cultured</DescriptorName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">anticaner activity</Keyword>
<Keyword MajorTopicYN="N">rapamycin</Keyword>
<Keyword MajorTopicYN="N">semi-synthesis</Keyword>
<Keyword MajorTopicYN="N">triazole</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year>
<Month>04</Month>
<Day>17</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2018</Year>
<Month>09</Month>
<Day>16</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2018</Year>
<Month>09</Month>
<Day>26</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2018</Year>
<Month>10</Month>
<Day>26</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<PubMedPubDate PubStatus="medline"><Year>2019</Year>
<Month>4</Month>
<Day>9</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2018</Year>
<Month>10</Month>
<Day>26</Day>
<Hour>6</Hour>
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</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">30357890</ArticleId>
<ArticleId IdType="doi">10.1002/ardp.201800123</ArticleId>
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</pubmed>
<affiliations><list><country><li>République populaire de Chine</li>
</country>
<region><li>Fujian</li>
<li>Zhejiang</li>
</region>
<settlement><li>Fuzhou</li>
<li>Hangzhou</li>
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<tree><country name="République populaire de Chine"><region name="Fujian"><name sortKey="Huang, Qingwen" sort="Huang, Qingwen" uniqKey="Huang Q" first="Qingwen" last="Huang">Qingwen Huang</name>
</region>
<name sortKey="Chen, Xiaoming" sort="Chen, Xiaoming" uniqKey="Chen X" first="Xiaoming" last="Chen">Xiaoming Chen</name>
<name sortKey="Cheng, Yuanrong" sort="Cheng, Yuanrong" uniqKey="Cheng Y" first="Yuanrong" last="Cheng">Yuanrong Cheng</name>
<name sortKey="Huang, Jie" sort="Huang, Jie" uniqKey="Huang J" first="Jie" last="Huang">Jie Huang</name>
<name sortKey="Huang, Jie" sort="Huang, Jie" uniqKey="Huang J" first="Jie" last="Huang">Jie Huang</name>
<name sortKey="Huang, Qingwen" sort="Huang, Qingwen" uniqKey="Huang Q" first="Qingwen" last="Huang">Qingwen Huang</name>
<name sortKey="Huang, Xuehui" sort="Huang, Xuehui" uniqKey="Huang X" first="Xuehui" last="Huang">Xuehui Huang</name>
<name sortKey="Lv, Yubing" sort="Lv, Yubing" uniqKey="Lv Y" first="Yubing" last="Lv">Yubing Lv</name>
<name sortKey="Xie, Lijun" sort="Xie, Lijun" uniqKey="Xie L" first="Lijun" last="Xie">Lijun Xie</name>
<name sortKey="Ying, Jiayin" sort="Ying, Jiayin" uniqKey="Ying J" first="Jiayin" last="Ying">Jiayin Ying</name>
<name sortKey="Yu, Hui" sort="Yu, Hui" uniqKey="Yu H" first="Hui" last="Yu">Hui Yu</name>
<name sortKey="Zheng, Congshen" sort="Zheng, Congshen" uniqKey="Zheng C" first="Congshen" last="Zheng">Congshen Zheng</name>
</country>
</tree>
</affiliations>
</record>

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	Serveur d'exploration sur la rapamycine et les champignons
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Serveur d'exploration sur la rapamycine et les champignons

Synthesis and anticancer activity of novel rapamycin C-28 containing triazole moiety compounds.

Synthesis and anticancer activity of novel rapamycin C-28 containing triazole moiety compounds.

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