Multi-armed antibiotics for Gram-positive bacteria

Antibiotic resistance is a serious threat to public health. Here, we propose a multi-armed chemical scaffold (MACS) for antibiotic screening, which refers to multi-armed molecules (MAMs) consisting of a core unit and three or four arms, neither of which is active for pathogens. Based on a structure-activity relationship study of MAMs, we discover a class of multi-armed antibiotics (MAAs) with a core similar to ethylene (E), carbon atom (C), benzene (B), nitrogen atom (N), and triazine (T) and three or four 4-phenylbenzoic acid (PBA) arms, or a B core and three 4-vinylbenzoic acid (VBA) or 4-ethynylbenzoic acid (EBA) arms. They can selectively interact with Gram-positive bacteria and inhibit cell wall assembly by targeting the lipid carriers of cell wall biosyn-thesis. MAAs have excellent antibacterial activities against Gram-positive bacteria, including clinical multi -drug-resistant (MDR) isolates. Our study provides a chemical scaffold and identifies eight antibacterial lead compounds for the development of antibiotics.

Automated summary

We propose a multi-armed chemical scaffold (MACS) for antibiotc screening, consisting of a core unit and three or four arms. Through studying the structure-activity relationship of multi-armed molecules (MAMs), we discover a class of multi-armed antibiotics (MAAs) that can selectively interact with Gram-positive bacteria and inhibit cell wall assembly. MAAs have excellent antibacterial activities against Gram-positive bacteria, including clinical multi-drug-resistant isolates. Our study provides a chemical scaffold and identifies eight antibacterial lead compounds for antibiotic development.