A Novel Dicationic Boron Dipyrromethene-based Photosensitizer for Antimicrobial Photodynamic Therapy against Methicillin-Resistant Staphylococcus aureus.

Abstract:

BACKGROUND:We report herein the synthesis of a novel dicationic boron dipyrromethene derivative (compound 3) which is symmetrically substituted with two trimethylammonium styryl groups. METHODS:The antibacterial photodynamic activity of compound 3 was determined against sixteen methicillin-resistant Staphylococcus aureus (MRSA) strains, including four ATCC type strains (ATCC 43300, ATCC BAA-42, ATCC BAA-43, and ATCC BAA-44), two mutant strains [AAC(6')-APH(2") and RN4220/pUL5054], and ten non-duplicate clinical strains of hospital- and communityassociated MRSA. Upon light irradiation, the minimum bactericidal concentrations of compound 3 were in the range of 1.56-50 µM against all the sixteen MRSA strains. Interestingly, compound 3 was not only more active than an analogue in which the ammonium groups are not directly connected to the pconjugated system (compound 4), but also showed significantly higher (p < 0.05) antibacterial potency than the clinically approved photosensitizer methylene blue. The skin irritation of compound 3 during topical application was tested on human 3-D skin constructs and proven to be non-irritant in vivo at concentrations below 1.250 mM. In the murine MRSA infected wound study, the colony forming unit reduction of compound 3 + PDT group showed significantly (p < 0.05) higher value (>2.5 log10) compared to other test groups except for the positive control. CONCLUSION:In conclusion, the present study provides a scientific basis for future development of compound 3 as a potent photosensitizer for photodynamic therapy for MRSA wound infection.

journal_name

Curr Med Chem

authors

Dharmaratne P,Yu L,Wong RC,Chan BC,Lau KM,Wang B,Lau CB,Fung KP,Ng DK,Ip M

doi

10.2174/0929867328666201208095105

subject

Has Abstract

pub_date

2020-12-07 00:00:00

eissn

0929-8673

issn

1875-533X

pii

CMC-EPUB-112156

pub_type

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