Benzophenones: Novel natural agents which inhibits HIV and Candida

二苯甲酮：抑制艾滋病毒和念珠菌的新型天然药物

• 批准号: 8719942
• 负责人: Ramiro Mendonca Murata
• 金额: $ 24.14万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-29 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8719942
• 关键词: Acquired Immunodeficiency Syndrome; Affect; Antifungal Agents; Antiviral Agents; Attention; Bacteria; Benzophenones; Biological Factors; Biosensor; CCR5 gene; CXCR4 gene; Candida; Candida albicans; Cell Culture Techniques; Cell Line; Circular Dichroism; Clinical; Communicable Diseases; Data; Development; Disease; Drug resistance; Epidemic; Foundations; Fruit; Goals; HIV; HIV Envelope Protein gp120; HIV Infections; HIV-1; Imaging Techniques; Immunosuppressive Agents; Infection; Integration Host Factors; Investigation; Knowledge; Laboratories; Life; Malignant Neoplasms; Mammalian Cell; Mediating; Mentors; Mentorship; Microbial Biofilms; Modification; Molecular Target; New York; Opportunistic Infections; Pathway interactions; Peripheral Blood Mononuclear Cell; Phase; Phytochemical; Polysaccharides; Scanning Electron Microscopy; Spatial Distribution; Structure; Testing; Therapeutic; Therapeutic Agents; Therapeutic Index; Toxic effect; Training; United States National Institutes of Health; Universities; Vaccines; Viral; Virus; Virus Receptors; Waika Plum; antimicrobial; biophysical techniques; career; fluorescence imaging; fungus; immortalized cell; in vivo; microbial; microbicide; microorganism; novel; novel strategies; novel therapeutics; pandemic disease; pathogen; prevent; prospective; public health relevance; transmission process; virology

DESCRIPTION (provided by applicant): Acquired immunodeficiency syndrome (AIDS) is an immunosuppressive disease that results in life-threatening opportunistic infections and malignancies. Emphasis now has been placed on discovery and development of novel agents, including natural products, against viral and host factors involved in HIV transmission and infection, as well as therapeutics for opportunistic disease pathogens. Among these emerging therapies, natural products are receiving increased attention. Phytochemical investigations of the Rheedia brasiliensis' fruit resulted in the isolation and identification of new potentially bioactive benzophenones. The polyprenilated benzophenones have shown anti-microbial, anti-fungal and anti-HIV activity. However, the mechanism(s) of action of benzophenoes against both HIV and opportunistic infections, including Candida, has yet to be determined. The central objective is to identify the targets that mediate the activity of benzophenones on both HIV and the opportunistic microorganism Candida sp. and to identify the natural compounds with the highest therapeutic index. Mentored k99 phase: The mentored phase of the proposal will be carried out under the mentorship of Prof. Daniel Malamud and Prof. Simone Duarte at New York University. The goal of this phase is to evaluate the antiviral activity and toxicity of benzophenones on immortalized cell lines to establish the therapeutic index for both M-tropic and T-tropic strains of HIV-1; Aim 2) Identify and characterize specific molecular target(s) by which the benzophenones inhibit HIV infection through interaction with viral gp120 or mammalian cell receptors for the virus using circular dichroism, biosensor analysis and Aim 3) Evaluate and characterize the anti-fungal effect of benzophenones against C. albicans biofilms and determine how these agents affect the content and composition of the polysaccharide matrix, using a combination of fluorescence imaging techniques and Scanning Electron Microscopy. These studies will provide the structural data on modification of the biofilm matrix by the benzophenones, e.g. spatial distribution of biofilm matrix and fungi, and linkage composition of the polysaccharides. This training will provide expertise in virology, structure determination, and cell culture techniques. The acquired knowledge will provide the foundation for transition to an independent career. During the independent phase, I will continue my study with natural molecules to identify additional pathways that may contribute to prevent or treat infectious diseases and assess their potential in vivo.

描述（由申请人提供）：获得的免疫缺陷综合征（AIDS）是一种免疫抑制疾病，导致危及生命的机会性感染和恶性肿瘤。现在重点放在针对艾滋病毒传播和感染涉及的病毒和宿主因素以及机会性疾病病原体的治疗剂的发现和开发中，包括天然产物，包括天然产物。在这些新兴疗法中，天然产品正在受到越来越多的关注。对巴西利氏菌的水果的植物化学研究导致分离和鉴定新的潜在生物活性苯甲酮。多加生化的苯甲酮已显示出抗微生物，抗真菌和抗HIV活性。然而，苯并o的作用机理对艾滋病毒和机会性感染（包括念珠菌）的作用机制尚未确定。核心目标是确定介导苯甲酮对HIV和机会性微生物念珠菌念珠菌的活性的靶标。并确定具有最高治疗指数的天然化合物。指导K99阶段：该提案的指导阶段将在纽约大学丹尼尔·马拉穆德（Daniel Malamud）教授和西蒙妮·杜阿尔特（Simone Duarte）教授的指导下进行。该阶段的目的是评估苯甲酮在永生细胞系上的抗病毒活性和毒性，以建立HIV-1的M-热带和T-热带菌株的治疗指数；目标2）确定并表征特定的分子靶标，通过使用圆形二色性，生物传感器分析和目标，苯甲酮通过与病毒GP120或哺乳动物细胞受体相互作用来抑制HIV感染，以评估和表征对这些苯甲酸杆菌的抗真实性，并确定这些对这些氧化梭菌的抗真实性的影响，并确定这些对这些氧化梭菌的抗真实性的影响，并确定这些抗核心的抗真菌剂的抗真菌剂。矩阵，结合荧光成像技术和扫描电子显微镜。这些研究将提供有关苯甲酮修饰生物膜基质的结构数据，例如生物膜基质和真菌的空间分布以及多糖的连锁组成。该培训将在病毒学，结构确定和细胞培养技术方面提供专业知识。获得的知识将为过渡到独立职业的基础。在独立阶段，我将继续使用自然分子进行研究，以识别可能有助于预防或治疗传染病并评估其在体内潜力的其他途径。

项目成果

The changing role of HIV-associated oral candidiasis in the era of HAART.

HAART 时代 HIV 相关口腔念珠菌病的作用发生变化。

• 发表时间: 2015
• 期刊: Journal of the California Dental Association
• 作者: Patuwo,Christopher;Young,Keane;Lin,Meng;Pardi,Vanessa;Murata,RamiroM
• 通讯作者: Murata,RamiroM

β-Glucans (Saccharomyces cereviseae) Reduce Glucose Levels and Attenuate Alveolar Bone Loss in Diabetic Rats with Periodontal Disease.

• DOI: 10.1371/journal.pone.0134742
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Silva Vde O;Lobato RV;Andrade EF;de Macedo CG;Napimoga JT;Napimoga MH;Messora MR;Murata RM;Pereira LJ
• 通讯作者: Pereira LJ

Anti-HIV-1 activity of flavonoid myricetin on HIV-1 infection in a dual-chamber in vitro model.

• DOI: 10.1371/journal.pone.0115323
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Pasetto S;Pardi V;Murata RM
• 通讯作者: Murata RM

Isoflavonoids from Brazilian red propolis down-regulate the expression of cancer-related target proteins: A pharmacogenomic analysis.

巴西红蜂胶中的异黄酮类化合物下调癌症相关靶蛋白的表达：药物基因组学分析。

• DOI: 10.1002/ptr.6016
• 发表时间: 2018
• 期刊: Phytotherapy research : PTR
• 作者: Nani,BrunoDias;Franchin,Marcelo;Lazarini,JosyGoldoni;Freires,IrlanAlmeida;daCunha,MarcosGuilherme;Bueno-Silva,Bruno;deAlencar,SeverinoMatias;Murata,RamiroMendonça;Rosalen,PedroLuiz
• 通讯作者: Rosalen,PedroLuiz