Hydroxychalcone inhibitors of Streptococcus mutans glucosyl transferases and biofilms as potential anticaries agents.
Hydroxychalcone inhibitors of Streptococcus mutans glucosyl transferases and biofilms as potential anticaries agents.
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DOI：
10.1016/j.bmcl.2016.06.033
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发表时间：
2016-08-01
影响因子：
2.7
通讯作者：
Velu, Sadanandan E.
中科院分区：
文献类型：
--
作者：
Nijampatnam, Bhavitavya;Casals, Luke;Zheng, Ruowen;Wu, Hui;Velu, Sadanandan E.
变形链球菌是龋病发生发展的主要病原体，其形成生物膜的能力很强。这种疾病的理想疗法旨在选择性地抑制生物膜形成过程，同时保留口腔的天然细菌植物群。一些研究已经证明了黄酮醇对S。变形链球菌生物膜，并提出了通过其对S.变异葡糖基转移酶（Gtfs）。这些酶将蔗糖代谢成水不溶性和可溶性葡聚糖，这是龋齿发病机理的整体测量。大量研究表明，黄酮醇和多酚可以抑制GTF和生物膜形成在毫摩尔浓度。我们从S.变形菌生物膜测定。这些化合物中的几种在低微摩尔浓度下成为生物膜抑制剂。在A环上含有3-OH基团的查耳酮表现出对生物膜抑制的选择性。此外，我们合成了先导化合物的另外6种类似物，并评估了它们对S的潜在活性和选择性。变形杆菌生物膜从这些研究中鉴定的最具活性的化合物对生物膜的IC 50值为44μM，对生长的MIC 50值为468μM，显示对生物膜的选择性抑制>10倍。先导化合物对S.变形链球菌先导化合物在至少高达200 µM的浓度下也不会影响两种细菌（血链球菌和戈登链球菌）的生长，表明它可以选择性地抑制致龋生物膜，同时保持细菌和/或有益微生物的完整性。因此，无毒化合物在公共口腔健康体系中具有潜在的实用性。
Streptococcus mutans has been implicated as the major etiological agent in the initiation and the development of dental caries due to its robust capacity to form tenacious biofilms. Ideal therapeutics for this disease will aim to selectively inhibit the biofilm formation process while preserving the natural bacterial flora of the mouth. Several studies have demonstrated the efficacies of flavonols on S. mutans biofilms and have suggested the mechanism of action through their effect on S. mutans glucosyltransferases (Gtfs). These enzymes metabolize sucrose into water insoluble and soluble glucans, which are an integral measure of the dental caries pathogenesis. Numerous studies have shown that flavonols and polyphenols can inhibit Gtf and biofilm formation at millimolar concentrations. We have screened a group of 14 hydroxychalcones, synthetic precursors of flavonols, in an S. mutans biofilm assay. Several of these compounds emerged to be biofilm inhibitors at low micro-molar concentrations. Chalcones that contained a 3-OH group on ring A exhibited selectivity for biofilm inhibition. Moreover, we synthesized 6 additional analogs of the lead compound and evaluated their potential activity and selectivity against S. mutans biofilms. The most active compound identified from these studies had an IC50 value of 44µM against biofilm and MIC50 value of 468µM against growth displaying >10 fold selectivity inhibition towards biofilm. The lead compound displayed a dose dependent inhibition of S. mutans Gtfs. The lead compound also did not affect the growth of two commensal species (Streptococcus sanguinis and Streptococcus gordonii) at least up to 200 µM, indicating that it can selectively inhibit cariogenic biofilms, while leaving commensal and/or beneficial microbes intact. Thus non-toxic compounds have the potential utility in public oral health regimes.
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影响因子：
4.9
作者：
Koo, H;Rosalen, PL;Bowen, WH
通讯作者：
Bowen, WH
影响因子：
3.2
作者：
Koo, H.;Xiao, J.;Jeon, J. G.
通讯作者：
Jeon, J. G.
影响因子：
3.1
作者：
VACCASMITH, AM;JONES, CA;STINSON, MW
通讯作者：
STINSON, MW
新型二氢叶酸还原酶小分子抑制剂抑制变形链球菌
DOI：
10.1016/j.ijantimicag.2015.03.015
发表时间：
2015-08
影响因子：
10.8
作者：
Zhang Q;Nguyen T;McMichael M;Velu SE;Zou J;Zhou X;Wu H
通讯作者：
Wu H
影响因子：
4.2
作者：
Koo, H.;Duarte, S.;Vorsa, N.
通讯作者：
Vorsa, N.