一种用于抗甲氧西林金黄色葡萄球菌的抗菌光动力疗法的新型双阳离子硼二吡咯亚甲基光敏剂

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

Volume: 28 Issue: 21

关键词: 耐甲氧西林金黄色葡萄球菌、抗菌光动力疗法、二吡咯甲硼硼、鼠伤口感染模型、光敏剂、抗菌效力。

摘要:

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 nonduplicate clinical strains of hospital- and community-associated 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 n-conjugated 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.

Cite this article as:

A Novel Dicationic Boron Dipyrromethene-based Photosensitizer for Antimicrobial Photodynamic Therapy against Methicillin-Resistant Staphylococcus aureus, Current Medicinal Chemistry 2021; 28 (21) . https://dx.doi.org/10.2174/0929867328666201208095105