抗艾滋病药物，1. 从鞣酸中分离并鉴定出四种新型四没食子酰奎宁酸作为一类新的HIV逆转录酶抑制剂。

Anti-AIDS agents, 1. Isolation and characterization of four new tetragalloylquinic acids as a new class of HIV reverse transcriptase inhibitors from tannic acid.

作者信息

Nishizawa M, Yamagishi T, Dutschman G E, Parker W B, Bodner A J, Kilkuskie R E, Cheng Y C, Lee K H

机构信息

Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill 27599.

出版信息

J Nat Prod. 1989 Jul-Aug;52(4):762-8. doi: 10.1021/np50064a016.

DOI:10.1021/np50064a016

PMID:2478667

Abstract

Four new tetragalloylquinic acids, 3,5-di-O-galloyl-4-O-digalloylquinic acid, 3,4-di-O-galloyl-5-O-digalloylquinic acid, 3-O-digalloyl-4,5-di-O-galloylquinic acid, and 1,3,4,5-tetra-O-galloylquinic acid, were isolated and characterized from a commercial tannic acid as a new class of human immunodeficiency virus (HIV) reverse transcriptase (RT) inhibitor. Compounds 2, 3, and 4 inhibit HIV RT activity 90, 89, and 84% at 100 microM and 73, 70, and 63% at 30 microM, respectively. Compounds 2-5 also inhibit the HIV growth in cells in the range of 61-70% with low cytotoxicity at 25 microM. The HIV cell growth inhibitory effects of these compounds at 25 microM and 6.25 microM (44-57%) are comparable to their effects against the HIV RT at 30 microM and 10 microM, respectively. The inhibitory effect of 3 against DNA polymerases indicates that the selective antiviral action of 3 is determined by more than its action with HIV RT.

摘要

从市售单宁酸中分离并鉴定出四种新的四没食子酰奎尼酸，即3,5-二-O-没食子酰-4-O-二没食子酰奎尼酸、3,4-二-O-没食子酰-5-O-二没食子酰奎尼酸、3-O-二没食子酰-4,5-二-O-没食子酰奎尼酸和1,3,4,5-四-O-没食子酰奎尼酸，它们是一类新型的人类免疫缺陷病毒（HIV）逆转录酶（RT）抑制剂。化合物2、3和4在100微摩尔时分别抑制HIV RT活性90%、89%和84%，在30微摩尔时分别抑制73%、70%和63%。化合物2至5在25微摩尔时也能抑制细胞中的HIV生长，抑制率在61%至70%之间，且细胞毒性较低。这些化合物在25微摩尔和6.25微摩尔时对HIV细胞生长的抑制作用（44%至57%）分别与其在30微摩尔和10微摩尔时对HIV RT的作用相当。化合物3对DNA聚合酶的抑制作用表明，其选择性抗病毒作用不仅仅取决于它对HIV RT的作用。