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GOSSYPOL DERIVATIVES AS COVALENT CARRIERS OF ANTIVIRALS

作为抗病毒药物共价载体的棉酚衍生物

基本信息

批准号：
3454572
负责人：
ROBERT ROYER
金额：
$ 10.4万
依托单位：
UNIVERSITY OF NEW MEXICO
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-09-30 至 1993-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3454572
关键词：
Alphaherpesvirinae T lymphocyte acyclovir antiAIDS agent antiviral agents covalent bond drug design /synthesis /production drug vehicle esterification human immunodeficiency virus 1 human tissue ribavirin tissue /cell culture virus envelope

项目摘要

The objective of this research project is to develop new antiviral drugs useful for treatment of disease caused by enveloped viruses. Included among these diseases is Acquired Immunodeficiency Syndrome. The rationale for the proposed approach is to utilize intrinsic properties of gossypol derivatives as antiviral agents against enveloped viruses and as agents with affinities for the envelope membranes. Gossypol derivatives will be convalently attached to known antiviral drugs in order to develop a new set of drugs in which the gossypol moiety is both a vehicle for drug delivery and a separate drug which may exert a synergistic effect after hydrolysis of the covalent adduct of gossypol derivative and antiviral drug. The specific aims are: 1) The esterify gossypol derivatives to promising antivirals against human immunodeficiency virus (HIV) and herpes simplex virus (HSV), such as aziodothymidine, ribavirin and acyclovir, and to test these conjugated derivatives for activity in vitro. 2) To attach gossypol derivatives to polypeptides which are known to be active against HIV or influenza virus, and to test these conjugated derivatives for activity in vitro. The major methodology in this study is the synthetic chemistry necessary to prepare various gossypol derivatives and to attach derivatives to known antivirals. Much of this synthetic chemistry has been developed already. In vitro studies of these new drugs will be carried out with HIV, using human T cells; with HSV-II, using Vero cells; and with influenza virus, using MDCK cells. This approach, which utilizes a retrovirus, a DNA virus, and an RNA virus, all of which are enveloped, should provide an indication whether these new covalently linked drugs are generally active against enveloped viruses or whether they exhibit specificity for certain enveloped viruses.

本研究项目的目标是开发新的抗病毒药物用于治疗由包膜病毒引起的疾病的药物。这些疾病包括获得性免疫缺陷综合征所提议方法的基本原理是利用棉酚衍生物作为抗病毒剂的内在性质抗包膜病毒，并作为与被膜棉酚衍生物将被广泛应用连接到已知的抗病毒药物，以开发一套新的其中棉酚部分既是药物载体的药物递送和可能发挥协同作用的单独药物在棉酚衍生物的共价加合物水解后，抗病毒药物具体目标是： 1)从棉酚衍生物到有前途的抗病毒药物艾滋病毒和单纯疱疹病毒 - 病毒（HSV），如偶氮碘胸苷、利巴韦林和阿昔洛韦，以及以测试这些缀合衍生物的体外活性。 2)将棉酚衍生物连接到多肽上，已知对HIV或流感病毒有活性，并测试这些共轭衍生物的体外活性。本研究的主要方法是合成化学制备各种棉酚衍生物和连接已知抗病毒药物的衍生物。这些合成化学已经被开发出来了。这些新药的体外研究将使用人类T细胞对HIV进行治疗;使用HSV-II，使用Vero细胞;和流感病毒，使用MDCK细胞。这利用逆转录病毒、DNA病毒和RNA的方法所有病毒都有包膜，这些新的共价连接的药物是否具有是否对包膜病毒有特异性，某些有包膜的病毒