DEVELOPMENT OF A MARINE ANTI-PLAQUE COMPOUND

流行病学调查显示，美国平均有50%的成年人口患有牙周炎，牙周炎可导致多种危及生命的疾病，如心脏病。由于牙周炎是由菌斑引起的，而菌斑是由各种细菌组成的，从理论上讲，抗菌药物应该对牙周炎有效。大多数抗菌斑化合物，如三氯生、氯己烯和氟，都是卤化的。海洋微生物可以产生含有氯和溴等卤素的化合物，因此可以成为发现抗菌斑化合物的重要资源。最近，从150种海洋微生物中提取的4800种提取物对伴生放线菌、粘性放线菌和变形链球菌的抗菌活性进行了筛选。其中一种微生物的提取物APP214被发现对这些微生物具有良好的抑制和杀菌活性。这项建议的具体目的是分离、鉴定和表征APP214衍生的生物活性成分(就抗菌效果和毒性而言)。在第二阶段，将对候选化合物(S)进行药物和组合化学，以最大限度地提高对口腔相关微生物的有效性和实质性。在第三阶段，铅抗菌斑化合物将与缅因州的Tom‘s公司、吉列公司或高露洁棕榄公司等工业合作伙伴一起商业化。建议的商业应用：目前还没有真正有效的抗牙周炎产品，既方便使用，又吸引消费者。一种对口腔生物膜(牙菌斑)有效和实质性的产品将在美国和国际上具有巨大的市场潜力。

Epidemiological surveys indicate that an average of 50% of the adult population of the United States (US) has gingivitis and that gingivitis can lead to a number of life threatening illnesses such as heart disease. Since gingivitis is caused by plaque and plaque is composed of various kinds of bacteria, in theory antimicrobial agents should be effective against gingivitis. Most anti-plaque compounds, e.g. triclosan, chlorohexidene and fluorine, are halogenated. Marine microorganisms, which can generate compounds that integrate halogens such as chlorine and bromine, can thus be an important resource for the discovery of anti-plaque compounds. Recently 4,800 extracts derived from 150 marine microorganisms were screened for anti-microbial activity against - Haemophilus actinomycetemcomitans, Actinomyces viscosus, and Streptococcus mutans. The extract of one organism, APP214, was found to have excellent inhibitory and bactericidal activity against these microorganisms. The specific aims of this proposal are to isolate, identify and characterize (in terms of antimicrobial efficacy and toxicity) the bioactive components derived from APP214. In Phase II, medicinal and combinatorial chemistry will be performed on the candidate compound(s) to maximize effectiveness and substantivity against orally-relevant microorganisms. In Phase III, the lead anti-plaque compound will be commercialized with an industrial partner, such as Tom's of Maine, Gillette or Colgate-Palmolive. PROPOSED COMMERCIAL APPLICATIONS: There is currently no truly efficacious anti-gingivitis product that is also both convenient to use and appealing to the consumer. A product that is effective and substantive against oral biofilms (dental plaque) will have a significant market potential in the United States and internationally.