A diversity-oriented rhodamine library for wide-spectrum bactericidal agents with low inducible resistance against resistant pathogens

Abstract

Antimicrobial resistance is a public health emergency and warrants coordinated global efforts. Challenge is that no alternative molecular platform has been identified for discovery of abundant antimicrobial hit compounds. Xanthene libraries have been screened for bioactive compounds. However, the potentially accessible chemistry space of xanthene dyes is limited by the existing xanthene synthesis. Herein we report a mild one-step synthesis, which permits late-stage introduction of a xanthene moiety onto i.e. natural products, pharmaceuticals, and bioactive compounds and construction of a focused library of rhodamine dyes exhibiting facile functional, topographical and stereochemical diversity. In vitro screening yields 37 analogs with mid-to-high bactericidal activity against WHO priority drug-resistant pathogens. These findings suggest that synthetic dye libraries exhibiting high structural diversity is a feasible chemical space combating antibacterial resistance, to complement the natural sources.

Real-time detection of single-molecule reaction by plasmon-enhanced spectroscopy

“…During laser illumination, the ensuing cascade ring-opening and decarboxylation processes result in structure III with a slightly red-shifted fluorescence band and unchanged xanthene resonant Raman frequencies, which are consistent with our density functional theory (DFT) calculations ( fig. S9) and the literature (36). Last, as shown in Fig.…”

Zinc-doped Prussian blue enhances photothermal clearance of Staphylococcus aureus and promotes tissue repair in infected wounds

“…At high Van concentrations (160 mg kg −1 day −1 ), the biochemical measures of renal function are significantly higher ( P < 0.001) than those of the corresponding control, including blood urea nitrogen (BUN), creatinine (CR) and uric acid (UA), indicating certain nephrotoxicity 33 . Additionally, although Van is typically used as the last resort, Van-resistant pathogens are now widespread 34,35 .…”

Recent advances in construction of small molecule-based fluorophore-drug conjugates

“… Besides, fluorophores not only are useful in detection but also can act as a drug to achieve good inhibitions. Yang and coworkers [ 78 ] constructed a xanthene-derivative fluorophore library and found 37 analogs with mild-to-high bactericidal activities. Some NIR dyes, including diketopyrrolopyrrole (DPP) and diiodostyryl bodipy (DBHA), belong to photosensitizers capable of drug monitoring and synergistic cancer therapy [ 79 , 80 ].…”