Synthesis, antimicrobial evaluation, and molecular modelling studies of Niclosamide derivatives as biotin carboxylase inhibitors. | ||
| Azhar International Journal of Pharmaceutical and Medical Sciences | ||
| Article 4, Volume 3, Issue 1, January 2023, Pages 44-57 PDF (1.39 M) | ||
| Document Type: Original research articles | ||
| DOI: 10.21608/aijpms.2022.129287.1120 | ||
| Authors | ||
| Magda MF Ismail* 1; Tamer Nasr2, 3; Abeer Saeed2; Yousry A Ammar4 | ||
| 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt | ||
| 2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Helwan, Cairo, Egypt | ||
| 3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, MTI University, Cairo, Egypt | ||
| 4Department of Chemistry, Faculty of Science, Al-Azhar University, Cairo, Egypt | ||
| Abstract | ||
| New Niclosamide Schiff’s bases and Niclosamide esters were synthesized and evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacterial strains in addition to fungal strains. Moreover, the antimicrobial activity of the target compounds against the resistant bacterial strains MRSA10 and MRSA12 was evaluated. Minimum inhibition concentration (MIC) values of the target compounds were determined to evaluate their antimicrobial activities. Niclosamide esters 4, 5 and 6 displayed remarkable activities against MRSA12 (MIC ≤ 4.03 μM) and moderate activities against C. albicans (MIC 7.8-31.25 μM). Strong antibacterial activities were elicited by Niclosamide esters 4 and 5 against B. subtilis (MIC 1.95 μM, 3.90 μM; respectively). Docking studies demonstrated the ability of the target compounds to bind with the active site of the microbial biotin carboxylase. Furthermore, physicochemical properties and ADME calculations indicated that the target compounds are available by oral route, with no blood–brain barrier (BBB) permeation. This study demonstrated that Niclosamide esters are potent antimicrobial agents against Gram-positive and resistant MRSA12 bacterial strains and were safe towards the normal human cell line (WI-38). | ||
| Keywords | ||
| Niclosamide esters; Niclosamide Shiff’s bases; Biotin carboxylase; Antimicrobial; Docking; Cytotoxicity | ||
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