The Research of New Inhibitors of Bacterial Methionine Aminopeptidase by Structure Based Virtual Screening Approach of ZINC DATABASE and In Vitro Validation.
Identifieur interne : 000243 ( PubMed/Curation ); précédent : 000242; suivant : 000244The Research of New Inhibitors of Bacterial Methionine Aminopeptidase by Structure Based Virtual Screening Approach of ZINC DATABASE and In Vitro Validation.
Auteurs : Hanane Boucherit [Algérie] ; Abdelouahab Chikhi [Algérie] ; Abderrahmane Bensegueni [Algérie] ; Amina Merzoug [Algérie] ; Jean-Michel Bolla [France]Source :
- Current computer-aided drug design [ 1875-6697 ] ; 2020.
Abstract
BACKGROUND
The great emergence of multi-resistant bacterial strains and the low renewal of antibiotics molecules are leading human and veterinary medicine to certain therapeutic impasses. Therefore, there is an urgent need to find new therapeutic alternatives including new molecules in the current treatments of infectious diseases. Methionine aminopeptidase (MetAP) is a promising target for developing new antibiotics because it is essential for bacterial survival.
OBJECTIVE
To screen for potential MetAP inhibitors by in silico virtual screening of the ZINC database and evaluate the best potential lead molecules by in vitro studies.
METHODS
We have considered 200,000 compounds from the ZINC database for virtual screening with FlexX software to identify potential inhibitors against bacterial MetAP. Nine chemical compounds of the top hits predicted were purchased and evaluated in vitro. The antimicrobial activity of each inhibitor of MetAP was tested by the disc-diffusion assay against one Gram-positive (Staphylococcus aureus) and two Gram-negative (Escherichia coli & Pseudomonas aeruginosa) bacteria. Among the studied compounds, compounds ZINC04785369 and ZINC03307916 showed promising antibacterial activity. To further characterize their efficacy, the minimum inhibitory concentration was determined for each compound by the microdilution method which showed significant results.
RESULTS
These results suggest compounds ZINC04785369 and ZINC03307916 as promising molecules for developing MetAP inhibitors.
CONCLUSION
Furthermore, they could therefore serve as lead molecules for further chemical modifications to obtain clinically useful antibacterial agents.
DOI: 10.2174/1573409915666190617165643
PubMed: 31244429
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000244
Links to Exploration step
pubmed:31244429Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The Research of New Inhibitors of Bacterial Methionine Aminopeptidase by Structure Based Virtual Screening Approach of ZINC DATABASE and In Vitro Validation.</title><author><name sortKey="Boucherit, Hanane" sort="Boucherit, Hanane" uniqKey="Boucherit H" first="Hanane" last="Boucherit">Hanane Boucherit</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1, Algeria.</nlm:affiliation><country xml:lang="fr">Algérie</country><wicri:regionArea>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1</wicri:regionArea></affiliation></author><author><name sortKey="Chikhi, Abdelouahab" sort="Chikhi, Abdelouahab" uniqKey="Chikhi A" first="Abdelouahab" last="Chikhi">Abdelouahab Chikhi</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1, Algeria.</nlm:affiliation><country xml:lang="fr">Algérie</country><wicri:regionArea>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1</wicri:regionArea></affiliation></author><author><name sortKey="Bensegueni, Abderrahmane" sort="Bensegueni, Abderrahmane" uniqKey="Bensegueni A" first="Abderrahmane" last="Bensegueni">Abderrahmane Bensegueni</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1, Algeria.</nlm:affiliation><country xml:lang="fr">Algérie</country><wicri:regionArea>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1</wicri:regionArea></affiliation></author><author><name sortKey="Merzoug, Amina" sort="Merzoug, Amina" uniqKey="Merzoug A" first="Amina" last="Merzoug">Amina Merzoug</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1, Algeria.</nlm:affiliation><country xml:lang="fr">Algérie</country><wicri:regionArea>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1</wicri:regionArea></affiliation></author><author><name sortKey="Bolla, Jean Michel" sort="Bolla, Jean Michel" uniqKey="Bolla J" first="Jean-Michel" last="Bolla">Jean-Michel Bolla</name><affiliation wicri:level="1"><nlm:affiliation>Aix Marseille University, INSERM, SSA, MCT, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix Marseille University, INSERM, SSA, MCT, Marseille</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:31244429</idno><idno type="pmid">31244429</idno><idno type="doi">10.2174/1573409915666190617165643</idno><idno type="wicri:Area/PubMed/Corpus">000244</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000244</idno><idno type="wicri:Area/PubMed/Curation">000243</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000243</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The Research of New Inhibitors of Bacterial Methionine Aminopeptidase by Structure Based Virtual Screening Approach of ZINC DATABASE and In Vitro Validation.</title><author><name sortKey="Boucherit, Hanane" sort="Boucherit, Hanane" uniqKey="Boucherit H" first="Hanane" last="Boucherit">Hanane Boucherit</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1, Algeria.</nlm:affiliation><country xml:lang="fr">Algérie</country><wicri:regionArea>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1</wicri:regionArea></affiliation></author><author><name sortKey="Chikhi, Abdelouahab" sort="Chikhi, Abdelouahab" uniqKey="Chikhi A" first="Abdelouahab" last="Chikhi">Abdelouahab Chikhi</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1, Algeria.</nlm:affiliation><country xml:lang="fr">Algérie</country><wicri:regionArea>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1</wicri:regionArea></affiliation></author><author><name sortKey="Bensegueni, Abderrahmane" sort="Bensegueni, Abderrahmane" uniqKey="Bensegueni A" first="Abderrahmane" last="Bensegueni">Abderrahmane Bensegueni</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1, Algeria.</nlm:affiliation><country xml:lang="fr">Algérie</country><wicri:regionArea>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1</wicri:regionArea></affiliation></author><author><name sortKey="Merzoug, Amina" sort="Merzoug, Amina" uniqKey="Merzoug A" first="Amina" last="Merzoug">Amina Merzoug</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1, Algeria.</nlm:affiliation><country xml:lang="fr">Algérie</country><wicri:regionArea>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1</wicri:regionArea></affiliation></author><author><name sortKey="Bolla, Jean Michel" sort="Bolla, Jean Michel" uniqKey="Bolla J" first="Jean-Michel" last="Bolla">Jean-Michel Bolla</name><affiliation wicri:level="1"><nlm:affiliation>Aix Marseille University, INSERM, SSA, MCT, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix Marseille University, INSERM, SSA, MCT, Marseille</wicri:regionArea></affiliation></author></analytic><series><title level="j">Current computer-aided drug design</title><idno type="eISSN">1875-6697</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>The great emergence of multi-resistant bacterial strains and the low renewal of antibiotics molecules are leading human and veterinary medicine to certain therapeutic impasses. Therefore, there is an urgent need to find new therapeutic alternatives including new molecules in the current treatments of infectious diseases. Methionine aminopeptidase (MetAP) is a promising target for developing new antibiotics because it is essential for bacterial survival.</p></div><div type="abstract" xml:lang="en"><p><b>OBJECTIVE</b></p><p>To screen for potential MetAP inhibitors by in silico virtual screening of the ZINC database and evaluate the best potential lead molecules by in vitro studies.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>We have considered 200,000 compounds from the ZINC database for virtual screening with FlexX software to identify potential inhibitors against bacterial MetAP. Nine chemical compounds of the top hits predicted were purchased and evaluated in vitro. The antimicrobial activity of each inhibitor of MetAP was tested by the disc-diffusion assay against one Gram-positive (Staphylococcus aureus) and two Gram-negative (Escherichia coli & Pseudomonas aeruginosa) bacteria. Among the studied compounds, compounds ZINC04785369 and ZINC03307916 showed promising antibacterial activity. To further characterize their efficacy, the minimum inhibitory concentration was determined for each compound by the microdilution method which showed significant results.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>These results suggest compounds ZINC04785369 and ZINC03307916 as promising molecules for developing MetAP inhibitors.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>Furthermore, they could therefore serve as lead molecules for further chemical modifications to obtain clinically useful antibacterial agents.</p></div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">31244429</PMID><DateRevised><Year>2020</Year><Month>09</Month><Day>04</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1875-6697</ISSN><JournalIssue CitedMedium="Internet"><Volume>16</Volume><Issue>4</Issue><PubDate><Year>2020</Year></PubDate></JournalIssue><Title>Current computer-aided drug design</Title><ISOAbbreviation>Curr Comput Aided Drug Des</ISOAbbreviation></Journal><ArticleTitle>The Research of New Inhibitors of Bacterial Methionine Aminopeptidase by Structure Based Virtual Screening Approach of ZINC DATABASE and In Vitro Validation.</ArticleTitle><Pagination><MedlinePgn>389-401</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.2174/1573409915666190617165643</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">The great emergence of multi-resistant bacterial strains and the low renewal of antibiotics molecules are leading human and veterinary medicine to certain therapeutic impasses. Therefore, there is an urgent need to find new therapeutic alternatives including new molecules in the current treatments of infectious diseases. Methionine aminopeptidase (MetAP) is a promising target for developing new antibiotics because it is essential for bacterial survival.</AbstractText><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">To screen for potential MetAP inhibitors by in silico virtual screening of the ZINC database and evaluate the best potential lead molecules by in vitro studies.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">We have considered 200,000 compounds from the ZINC database for virtual screening with FlexX software to identify potential inhibitors against bacterial MetAP. Nine chemical compounds of the top hits predicted were purchased and evaluated in vitro. The antimicrobial activity of each inhibitor of MetAP was tested by the disc-diffusion assay against one Gram-positive (Staphylococcus aureus) and two Gram-negative (Escherichia coli & Pseudomonas aeruginosa) bacteria. Among the studied compounds, compounds ZINC04785369 and ZINC03307916 showed promising antibacterial activity. To further characterize their efficacy, the minimum inhibitory concentration was determined for each compound by the microdilution method which showed significant results.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">These results suggest compounds ZINC04785369 and ZINC03307916 as promising molecules for developing MetAP inhibitors.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Furthermore, they could therefore serve as lead molecules for further chemical modifications to obtain clinically useful antibacterial agents.</AbstractText><CopyrightInformation>Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Boucherit</LastName><ForeName>Hanane</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1, Algeria.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chikhi</LastName><ForeName>Abdelouahab</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1, Algeria.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bensegueni</LastName><ForeName>Abderrahmane</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1, Algeria.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Merzoug</LastName><ForeName>Amina</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, Mentouri Brothers University, Constantine 1, Algeria.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bolla</LastName><ForeName>Jean-Michel</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>Aix Marseille University, INSERM, SSA, MCT, Marseille, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United Arab Emirates</Country><MedlineTA>Curr Comput Aided Drug Des</MedlineTA><NlmUniqueID>101265750</NlmUniqueID><ISSNLinking>1573-4099</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Flex X</Keyword><Keyword MajorTopicYN="N">Methionine aminopeptidase</Keyword><Keyword MajorTopicYN="N">antibacterial agents</Keyword><Keyword MajorTopicYN="N">screening assistant</Keyword><Keyword MajorTopicYN="N">virtual screening</Keyword><Keyword MajorTopicYN="N">zinc database</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>01</Month><Day>28</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>04</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>05</Month><Day>06</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>6</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>6</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>6</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31244429</ArticleId><ArticleId IdType="pii">CAD-EPUB-98904</ArticleId><ArticleId IdType="doi">10.2174/1573409915666190617165643</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/MaghrebDataLibMedV2/Data/PubMed/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000243 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Curation/biblio.hfd -nk 000243 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= MaghrebDataLibMedV2
|flux= PubMed
|étape= Curation
|type= RBID
|clé= pubmed:31244429
|texte= The Research of New Inhibitors of Bacterial Methionine Aminopeptidase by Structure Based Virtual Screening Approach of ZINC DATABASE and In Vitro Validation.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Curation/RBID.i -Sk "pubmed:31244429" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Curation/biblio.hfd \
| NlmPubMed2Wicri -a MaghrebDataLibMedV2
| This area was generated with Dilib version V0.6.38. |  |