Synthesis and antibacterial activity of emodin and its derivatives against methicillin-resistant Staphylococcus aureus

Synthesis of the antibacterial emodin was improved using Friedel-Crafts acylation as a key step leading to 37% overall yield. In addition, 21 analogues were synthesized by structural modification of the hydroxyl and methyl groups, as well as the aromatic ring of emodin. Antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and cytotoxicity against noncancerous Vero cells were evaluated. A structure-activity relationship (SAR) study indicated that the hydroxyl groups and the methyl group in the emodin skeleton were crucial for anti-MRSA activity. Furthermore, the presence of an iodine atom or ethylamino group on the aromatic ring enhanced the anti-MRSA activity with higher selectivity indices, while derivatives containing bromine, chlorine atoms or quaternary ammonium salt were as active as emodin. The quaternary ammonium group on the aromatic ring also led to non-cytotoxicity against Vero cells. (C) 2019 Elsevier Ltd. All rights reserved.