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Novel Leu-Val Based Dipeptide as Antimicrobial and Antimalarial Agents: Synthesis and Molecular Docking

The increase of antimicrobial resistance (AMR) and antimalarial resistance are complex and severe health issues today, as many microbial strains have become resistant to market drugs. The choice for the synthesis of new dipeptide-carboxamide derivatives is as a result of their wide biological proper...

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Autores principales: Ezugwu, James A., Okoro, Uchechukwu C., Ezeokonkwo, Mercy A., Bhimapaka, China R., Okafor, Sunday N., Ugwu, David I., Ekoh, Ogechi C., Attah, Solomon I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732421/
https://www.ncbi.nlm.nih.gov/pubmed/33330372
http://dx.doi.org/10.3389/fchem.2020.583926
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author Ezugwu, James A.
Okoro, Uchechukwu C.
Ezeokonkwo, Mercy A.
Bhimapaka, China R.
Okafor, Sunday N.
Ugwu, David I.
Ekoh, Ogechi C.
Attah, Solomon I.
author_facet Ezugwu, James A.
Okoro, Uchechukwu C.
Ezeokonkwo, Mercy A.
Bhimapaka, China R.
Okafor, Sunday N.
Ugwu, David I.
Ekoh, Ogechi C.
Attah, Solomon I.
author_sort Ezugwu, James A.
collection PubMed
description The increase of antimicrobial resistance (AMR) and antimalarial resistance are complex and severe health issues today, as many microbial strains have become resistant to market drugs. The choice for the synthesis of new dipeptide-carboxamide derivatives is as a result of their wide biological properties such as antimicrobial, anti-inflammatory, and antioxidant activities. The condensation reaction of substituted benzenesulphonamoyl pentanamides with the carboxamide derivatives using peptide coupling reagents gave targeted products (8a-j). The in silico antimalarial and antibacterial studies showed good interactions of the compounds with target protein residues and a higher dock score in comparison with standard drugs. In the in vivo study, compound 8j was the most potent antimalarial agent with 61.90% inhibition comparable with 67% inhibition for Artemisinin. In the in vitro antimicrobial activity, compounds 8a and 8b (MIC 1.2 × 10(−3) M and 1.1 × 10(−3) M) were most potent against S. aureus; compound 8a, 8b, and 8j with MIC 6.0 × 10(−3) M, 5.7 × 10(−4) M, and 6.5 × 10(−4) M, respectively, were the most active against B. subtilis; compound 8b (MIC 9.5 × 10(−4) M) was most active against E.coli while 8a, 8b and 8d were the most active against S. typhi. Compounds 8c and 8h (MIC 1.3 × 10(−3) M) each were the most active against C. albicans, while compound 8b (MIC 1.3 × 10(−4) M) was most active against A. niger.
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spelling pubmed-77324212020-12-15 Novel Leu-Val Based Dipeptide as Antimicrobial and Antimalarial Agents: Synthesis and Molecular Docking Ezugwu, James A. Okoro, Uchechukwu C. Ezeokonkwo, Mercy A. Bhimapaka, China R. Okafor, Sunday N. Ugwu, David I. Ekoh, Ogechi C. Attah, Solomon I. Front Chem Chemistry The increase of antimicrobial resistance (AMR) and antimalarial resistance are complex and severe health issues today, as many microbial strains have become resistant to market drugs. The choice for the synthesis of new dipeptide-carboxamide derivatives is as a result of their wide biological properties such as antimicrobial, anti-inflammatory, and antioxidant activities. The condensation reaction of substituted benzenesulphonamoyl pentanamides with the carboxamide derivatives using peptide coupling reagents gave targeted products (8a-j). The in silico antimalarial and antibacterial studies showed good interactions of the compounds with target protein residues and a higher dock score in comparison with standard drugs. In the in vivo study, compound 8j was the most potent antimalarial agent with 61.90% inhibition comparable with 67% inhibition for Artemisinin. In the in vitro antimicrobial activity, compounds 8a and 8b (MIC 1.2 × 10(−3) M and 1.1 × 10(−3) M) were most potent against S. aureus; compound 8a, 8b, and 8j with MIC 6.0 × 10(−3) M, 5.7 × 10(−4) M, and 6.5 × 10(−4) M, respectively, were the most active against B. subtilis; compound 8b (MIC 9.5 × 10(−4) M) was most active against E.coli while 8a, 8b and 8d were the most active against S. typhi. Compounds 8c and 8h (MIC 1.3 × 10(−3) M) each were the most active against C. albicans, while compound 8b (MIC 1.3 × 10(−4) M) was most active against A. niger. Frontiers Media S.A. 2020-11-24 /pmc/articles/PMC7732421/ /pubmed/33330372 http://dx.doi.org/10.3389/fchem.2020.583926 Text en Copyright © 2020 Ezugwu, Okoro, Ezeokonkwo, Bhimapaka, Okafor, Ugwu, Ekoh and Attah. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Ezugwu, James A.
Okoro, Uchechukwu C.
Ezeokonkwo, Mercy A.
Bhimapaka, China R.
Okafor, Sunday N.
Ugwu, David I.
Ekoh, Ogechi C.
Attah, Solomon I.
Novel Leu-Val Based Dipeptide as Antimicrobial and Antimalarial Agents: Synthesis and Molecular Docking
title Novel Leu-Val Based Dipeptide as Antimicrobial and Antimalarial Agents: Synthesis and Molecular Docking
title_full Novel Leu-Val Based Dipeptide as Antimicrobial and Antimalarial Agents: Synthesis and Molecular Docking
title_fullStr Novel Leu-Val Based Dipeptide as Antimicrobial and Antimalarial Agents: Synthesis and Molecular Docking
title_full_unstemmed Novel Leu-Val Based Dipeptide as Antimicrobial and Antimalarial Agents: Synthesis and Molecular Docking
title_short Novel Leu-Val Based Dipeptide as Antimicrobial and Antimalarial Agents: Synthesis and Molecular Docking
title_sort novel leu-val based dipeptide as antimicrobial and antimalarial agents: synthesis and molecular docking
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732421/
https://www.ncbi.nlm.nih.gov/pubmed/33330372
http://dx.doi.org/10.3389/fchem.2020.583926
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