DEVELOPMENT OF A MARINE ANTI-PLAQUE COMPOUND

流行病学调查显示，美国平均50%的成年人患有牙龈炎，牙龈炎可导致许多危及生命的疾病，如心脏病。由于牙龈炎是由牙菌斑引起的，牙菌斑是由多种细菌组成的，理论上抗菌药物对牙龈炎应该是有效的。大多数抗菌斑化合物，如三氯生、氯己二烯和氟，都是卤化的。海洋微生物可以产生整合氯和溴等卤素的化合物，因此可以成为发现抗斑块化合物的重要资源。最近，从150种海洋微生物中提取的4800种提取物对放线菌嗜血杆菌、粘胶放线菌和变形链球菌的抑菌活性进行了筛选。其中一种生物的提取物APP214对这些微生物具有良好的抑制和杀菌活性。本提案的具体目的是分离、鉴定和表征（在抗菌功效和毒性方面）来自APP214的生物活性成分。在第二阶段，将对候选化合物进行药物化学和组合化学，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，主要的抗斑块化合物将与工业合作伙伴进行商业化，如缅因州的Tom's，吉列或高露洁棕榄。建议的商业应用：目前还没有真正有效的抗牙龈炎产品，既方便使用，又吸引消费者。一种对口腔生物膜（牙菌斑）有效且具有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.