Hydrogel-Encapsulated Biofilm Inhibitors Abrogate the Cariogenic Activity of Streptococcus mutans
Hydrogel-Encapsulated Biofilm Inhibitors Abrogate the Cariogenic Activity of Streptococcus mutans
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DOI：
10.1021/acs.jmedchem.3c00272
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发表时间：
2023-06-07
影响因子：
7.3
通讯作者：
Velu，Sadanandan E.
中科院分区：
文献类型：
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作者：
Ahirwar，Parmanand;Kozlovskaya，Veronika;Velu，Sadanandan E.
我们设计并合成了一种先前发现的生物膜抑制剂IIIC5的类似物，以改善溶解性，保持抑制活性，并促进将其包裹到pH响应型水凝胶微粒中。优化后的先导化合物HA5的溶解度提高到120.09μg/mL，抑制变形链球菌生物膜的IC50值为6.42μM，对口腔共生菌的生长没有影响，浓度提高了15倍。HA5与GTFB催化结构域共晶结构的测定表明，HA5的活性中心相互作用。HA5的抑制能力。突变Gtf和减少葡聚糖的产生已经被证明。将HA5包埋在水凝胶中形成的水凝胶包裹生物膜抑制剂(HEBI)选择性地抑制S。像HA5这样的突变生物膜。治疗OFS。与未经治疗的感染HA5或HEBI的变种大鼠相比，感染变种的大鼠的颊、沟和近端龋齿显著减少。
We designed and synthesized analogues of a previously identified biofilm inhibitorIIIC5to improve solubility, retain inhibitory activities, and to facilitate encapsulation into pH-responsive hydrogel microparticles. The optimized lead compoundHA5showed improved solubility of 120.09 μg/mL, inhibitedStreptococcus mutansbiofilm with an IC50value of 6.42 μM, and did not affect the growth of oral commensal species up to a 15-fold higher concentration. The cocrystal structure ofHA5with GtfB catalytic domain determined at 2.35 Å resolution revealed its active site interactions. The ability ofHA5to inhibitS. mutansGtfs and to reduce glucan production has been demonstrated. The hydrogel-encapsulated biofilm inhibitor (HEBI), generated by encapsulatingHA5in hydrogel, selectively inhibitedS. mutansbiofilms likeHA5. Treatment ofS. mutans-infected rats withHA5orHEBIresulted in a significant reduction in buccal, sulcal, and proximal dental caries compared to untreated, infected rats.