GOSSYPOL DERIVATIVES AS COVALENT CARRIERS OF ANTIVIRALS

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 方法，其利用逆转录病毒、DNA病毒和RNA病毒。 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

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.