Synthesis and In Vitro Photodynamic Activity of Cationic Boron Dipyrromethene-Based Photosensitizers against Methicillin-Resistant Staphylococcus aureus.

Priyanga Dharmaratne,Kit-Man Lau,Margaret Ip,Pui-Chi Lo,Ben C L Chan,Roy C H Wong,Dennis K P Ng,Clara B S Lau,Kwok-Pui Fung,Baiyan Wang,Jun Wang

doi:10.3390/biomedicines8060140

Abstract

A series of cationic boron dipyrromethene (BODIPY) derivatives were synthesized and characterized with various spectroscopic methods. Having the ability to generate singlet oxygen upon irradiation, these compounds could potentially serve as photosensitizers for antimicrobial photodynamic therapy. Of the five BODIPYs being examined, the dicationic aza-BODIPY analogue (compound 5) demonstrated the highest potency against a broad spectrum of clinically relevant methicillin-resistant Staphylococcus aureus (MRSA), including four ATCC-type strains (ATCC 43300, ATCC BAA-42, ATCC BAA-43, and ATCC BAA-44), two strains carrying specific antibiotic resistance mechanisms [-AAC(6’)-APH(2”) and RN4220/pUL5054], and ten non-duplicate clinical strains from hospital- and community-associated MRSAs of the important clonal types ST239, ST30, and ST59, which have previously been documented to be prevalent in Hong Kong and its neighboring countries. The in vitro anti-MRSA activity of compound 5 was achieved upon irradiation with near-infrared light (>610 nm) with minimal bactericidal concentrations (MBCs) ranging from 12.5 to 25 µM against the whole panel of MRSAs, except the hospital-associated MRSAs for which the MBCs were in the range of 50–100 µM. Compound 5 was significantly (p < 0.05) more potent than methylene blue, which is a clinically approved photosensitizer, indicating that it is a promising antimicrobial agent that is worthy of further investigation.

Highlights

Staphylococcus aureus remains the leading cause of hospital-associated infection and communityassociated infection around the globe, where a high proportion of these infections was caused by methicillin-resistant Staphylococcus aureus (MRSA) [1,2]
Knoevenagel condensation of compound 6 with the triethylglycol-substituted benzaldehyde 7 led to the formation of the distyryl analogue 8, which was N-methylated with CH3 I in DMF to afford the ammonium distyryl boron dipyrromethene (BODIPY) 1
A series of cationic BODIPY derivatives were synthesized and evaluated for their antimicrobial photodynamic activity against a broad spectrum of MRSAs. They exhibited a strong absorption in the near-infrared region (661–680 nm) and could generate singlet oxygen in DMF

Summary

Introduction

Staphylococcus aureus remains the leading cause of hospital-associated infection and communityassociated infection around the globe, where a high proportion of these infections was caused by methicillin-resistant Staphylococcus aureus (MRSA) [1,2]. Antimicrobial photodynamic therapy (aPDT) is such an alternative approach that is currently being explored as a potential therapeutic treatment option for various types of infections, including bacterial, fungal, viral, or even parasitic in nature [6,7,8,9,10]. It is conceptually simple and only requires a photosensitizer to generate reactive oxygen species (ROS), such as singlet oxygen, upon illumination with visible or near-infrared light [11]. The inactivation of microorganisms by this method is usually rapid [15] and the photosensitizers show limited or no resistance so far [16,17,18]

Methods

Results

Conclusion