Antimicrobial Photodynamic Therapy with Functionalized Fullerenes: Quantitative Structure-activity Relationships.
Antimicrobial Photodynamic Therapy with Functionalized Fullerenes: Quantitative Structure-activity Relationships.
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DOI：
10.4172/2157-7439.1000109
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发表时间：
2011-04-01
期刊：
影响因子：
--
通讯作者：
Hamblin MR
中科院分区：
文献类型：
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作者：
Mizuno K;Zhiyentayev T;Huang L;Khalil S;Nasim F;Tegos GP;Gali H;Jahnke A;Wharton T;Hamblin MR
光敏染料或光敏剂（PS）与可见光和氧气结合产生活性氧物质，其在称为光动力疗法（PDT）的过程中杀死细胞。抗微生物PDT采用对微生物细胞具有选择性的PS，是一种新的感染治疗方法。大多数抗微生物PS是基于四吡咯或吩噻嗪结构，其已被合成以携带季阳离子电荷或碱性氨基。然而，我们最近发现阳离子取代的富勒烯衍生物在用白色光照射后在杀死广谱微生物细胞方面非常有效。在本报告中，我们比较了一组新的合成富勒烯衍生物，具有碱性或季氨基作为抗微生物PS对革兰氏阳性菌（金黄色葡萄球菌），革兰氏阴性菌（大肠杆菌）和真菌（白色念珠菌）。用LogP和亲水亲脂平衡参数推导了定量结构-功能关系。具有非季胺基团的化合物倾向于在水中形成纳米聚集体，并且仅对S有效。金黄色。有效性的最重要的决定因素是季铵阳离子基团的数量增加，这些基团广泛分散在富勒烯笼周围，以最大限度地减少聚集。S. aureus最敏感; coli为中间型，C.白色念珠菌是测试的最耐药的物种。具有季铵化富勒烯的抗微生物PDT的高效性表明它们可以应用于治疗浅表感染（例如伤口和烧伤），其中光穿透到组织中是没有问题的。
Photosensitive dyes or photo sensitizers (PS) in combination with visible light and oxygen produce reactive oxygen species that kill cells in the process known as photodynamic therapy (PDT). Antimicrobial PDT employs PS that is selective for microbial cells and is a new treatment for infections. Most antimicrobial PS is based on tetrapyrrole or phenothiazinium structures that have been synthesized to carry quaternary cationic charges or basic amino groups. However we recently showed that cationic-substituted fullerene derivative were highly effective in killing a broad spectrum of microbial cells after illumination with white light. In the present report we compared a new group of synthetic fullerene derivatives that possessed either basic or quaternary amino groups as antimicrobial PS against Gram-positive (Staphylococcus aureus), Gram-negative bacteria (Escherichia coli) and fungi (Candida albicans). Quantitative structure-function relationships were derived with LogP and hydrophilic lipophilic balance parameters. Compounds with non-quaternary amino groups tended to form nanoaggregates in water and were only effective against S. aureus. The most important determinant of effectiveness was an increased number of quaternary cationic groups that were widely dispersed around the fullerene cage to minimize aggregation. S. aureus was most susceptible; E. coli was intermediate, while C. albicans was the most resistant species tested. The high effectiveness of antimicrobial PDT with quaternized fullerenes suggest they may have applications in treatment of superficial infections (for instance in wounds and burns) where light penetration into tissue is not problematic.