Synthesis, antimicrobial evaluation, and molecular modelling studies of Niclosamide derivatives as biotin carboxylase inhibitors.

Ismail, Magda MF; Nasr, Tamer; Saeed, Abeer; Ammar, Yousry A

doi:10.21608/aijpms.2022.129287.1120

Synthesis, antimicrobial evaluation, and molecular modelling studies of Niclosamide derivatives as biotin carboxylase inhibitors.

Document Type : Original research articles

Authors

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt

² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Helwan, Cairo, Egypt

³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, MTI University, Cairo, Egypt

⁴ Department of Chemistry, Faculty of Science, Al-Azhar University, Cairo, Egypt

10.21608/aijpms.2022.129287.1120

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).

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