The Research of New Inhibitors of Bacterial Methionine Aminopeptidase by Structure Based Virtual Screening Approach of ZINC DATABASE and In Vitro Validation.
Identifieur interne : 000575 ( Main/Exploration ); précédent : 000574; suivant : 000576The 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
Affiliations:
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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><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></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><affiliations><list><country><li>Algérie</li><li>France</li></country><region><li>Provence-Alpes-Côte d'Azur</li></region><settlement><li>Marseille</li></settlement></list><tree><country name="Algérie"><noRegion><name sortKey="Boucherit, Hanane" sort="Boucherit, Hanane" uniqKey="Boucherit H" first="Hanane" last="Boucherit">Hanane Boucherit</name></noRegion><name sortKey="Bensegueni, Abderrahmane" sort="Bensegueni, Abderrahmane" uniqKey="Bensegueni A" first="Abderrahmane" last="Bensegueni">Abderrahmane Bensegueni</name><name sortKey="Chikhi, Abdelouahab" sort="Chikhi, Abdelouahab" uniqKey="Chikhi A" first="Abdelouahab" last="Chikhi">Abdelouahab Chikhi</name><name sortKey="Merzoug, Amina" sort="Merzoug, Amina" uniqKey="Merzoug A" first="Amina" last="Merzoug">Amina Merzoug</name></country><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Bolla, Jean Michel" sort="Bolla, Jean Michel" uniqKey="Bolla J" first="Jean-Michel" last="Bolla">Jean-Michel Bolla</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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