1,8-Diaminonaphthalene-derived pharmacophore as potent anti-MRSA with dual DNA gyrase and topoisomerase IV inhibition
Husseiny, E., El menofy, N., El-Sebaey, S. (2022). 1,8-Diaminonaphthalene-derived pharmacophore as potent anti-MRSA with dual DNA gyrase and topoisomerase IV inhibition. EKB Journal Management System, 65(3), 1-17. doi: 10.21608/ejchem.2021.104410.4824
Ebtehal Mohammed Husseiny; Nagwan Galal El menofy; Samiha El-Sebaey. "1,8-Diaminonaphthalene-derived pharmacophore as potent anti-MRSA with dual DNA gyrase and topoisomerase IV inhibition". EKB Journal Management System, 65, 3, 2022, 1-17. doi: 10.21608/ejchem.2021.104410.4824
Husseiny, E., El menofy, N., El-Sebaey, S. (2022). '1,8-Diaminonaphthalene-derived pharmacophore as potent anti-MRSA with dual DNA gyrase and topoisomerase IV inhibition', EKB Journal Management System, 65(3), pp. 1-17. doi: 10.21608/ejchem.2021.104410.4824
Husseiny, E., El menofy, N., El-Sebaey, S. 1,8-Diaminonaphthalene-derived pharmacophore as potent anti-MRSA with dual DNA gyrase and topoisomerase IV inhibition. EKB Journal Management System, 2022; 65(3): 1-17. doi: 10.21608/ejchem.2021.104410.4824

1,8-Diaminonaphthalene-derived pharmacophore as potent anti-MRSA with dual DNA gyrase and topoisomerase IV inhibition

Egyptian Journal of Chemistry
Article 1, Volume 65, Issue 3, March 2022, Page 1-17  XML PDF (1.18 MB)
Document Type: Original Article
DOI: 10.21608/ejchem.2021.104410.4824
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Authors
Ebtehal Mohammed Husseiny email orcid 1; Nagwan Galal El menofy2; Samiha El-Sebaey3
1Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo, Egypt
2Department of Microbiology and Immunology, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo, Egypt
3Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo, Egypt
Abstract
1,8-Diaminonaphthalene was used as an active binucleophile from which some perimidines and (naphthalene-1,8-diyl)bis(heterocycles) were designed, prepared, and assessed for their antimicrobial activity against Staphylococcus aureus, Escherichia coli, different strains of methicillin-resistant Staphylococcus aureus (MRSA), and multidrug resistant (MDR) clinical isolates of Enterococcus faecium and Enterococcus faecalis. Compounds 1 and 6 exhibited significant antibacterial activity against Staphylococcus aureus with MIC values of 62.5 and 15.63 µg/mL. Additionally, compound 2 showed a remarkable antimicrobial activity against MRSA 1 (MIC = 62.5 µg/mL). Additionally, compound 6 exerted extremely potent antimicrobial effect towards all resistant strains with MIC values range of 31.25-62.5 µg/mL that is much more potent than reference drugs amoxicillin and cephalexin (MIC > 500 µg/mL). Furthermore, compounds 2, 3, and 6 displayed powerful antibiofilm activity against both Staphylococcus aureus and MRSA where compound 2 presented the most potent antibiofilm action among the tested compounds. To investigate the mechanism of action for compounds 2 and 6, inhibition of DNA gyrase together with topoisomerase IV were evaluated. Both compounds presented promising inhibitory action with IC50 at the micromolar range.
Keywords
antibiofilm; antimicrobial; DNA gyrase; MRSA; naphthalene; perimidine; topoisomerase IV
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