3-芳酰基-1,1-二氧代-1,4,2-苯并二硫嗪的合成、抗病毒及抗HIV-1整合酶活性

Synthesis, antiviral, and anti-HIV-1 integrase activities of 3-aroyl-1,1-dioxo-1,4,2-benzodithiazines.

作者信息

Brzozowski Zdzislaw, Saczewski Franciszek, Sanchez Tino, Kuo Chih-Ling, Gdaniec Maria, Neamati Nouri

机构信息

Department of Chemical Technology of Drugs, Medical University of Gdansk, Al. Gen. Hallera 107, 80-416 Gdansk, Poland.

出版信息

Bioorg Med Chem. 2004 Jul 1;12(13):3663-72. doi: 10.1016/j.bmc.2004.04.024.

DOI:10.1016/j.bmc.2004.04.024

PMID:15186851

Abstract

HIV-1 integrase (IN) is an essential enzyme for effective viral replication and is an attractive target for selective blockade of viral infection. Previously, we identified a series of sulfones, sulfonamides, and mercaptosalicylhydrazides (MBSAs) as IN inhibitors with antiviral activities in cell-based assays. In an effort to optimize a series of our active site directed lead compounds, we designed and synthesized novel benzodithiazines starting from MBSAs. In contrast to all reported IN inhibitors benzodithiazines are essentially nontoxic. Significant antiviral potency was only observed at concentration exceedingly higher than that required to inhibit purified IN.

摘要

HIV-1整合酶（IN）是病毒有效复制所必需的一种酶，也是选择性阻断病毒感染的一个有吸引力的靶点。此前，我们在基于细胞的检测中鉴定出一系列砜类、磺酰胺类和巯基水杨酰肼（MBSA）作为具有抗病毒活性的IN抑制剂。为了优化我们的一系列活性位点导向的先导化合物，我们从MBSA开始设计并合成了新型苯并二噻嗪。与所有已报道的IN抑制剂不同，苯并二噻嗪基本无毒。仅在浓度远高于抑制纯化IN所需浓度时才观察到显著的抗病毒效力。