Department of Life and Environmental Sciences, University of Cagliari, Monserrato, Italy.
Chemotherapy. 2012;58(4):299-307. doi: 10.1159/000343101. Epub 2012 Oct 31.
The degradative activity of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), termed ribonuclease H (RNase H), which hydrolyzes the RNA component of the heteroduplex RNA:DNA replication intermediate, is an excellent target for drug discovery. Anthraquinones (AQs) and their derivatives, which are common secondary metabolites occurring in bacteria, fungi, lichens and a large number of families in higher plants, have been reported to have several biological activities including that of inhibiting HIV-1 RT activities in biochemical assays.
We have assayed new AQ derivatives on HIV-1 RNase H activities in biochemical assays.
Six series of new AQ derivatives with various substituents at positions 1, 2, 3 and 4 of the AQ ring were tested, and new analogs able to inhibit HIV-1 RT-associated RNase H activity in the low micromolar range were found.
Our results demonstrate that AQ derivatives are promising anti-RNase H inhibitors.
人类免疫缺陷病毒 1 型（HIV-1）逆转录酶（RT）的降解活性，称为核糖核酸酶 H（RNase H），它水解 RNA：DNA 复制中间体的 RNA 成分，是药物发现的一个极好的靶点。蒽醌（AQs）及其衍生物是在细菌、真菌、地衣和高等植物的许多科中常见的次生代谢物，已被报道具有多种生物活性，包括抑制 HIV-1 RT 在生化测定中的活性。
我们在生化测定中检测了新的 AQ 衍生物对 HIV-1 RNase H 活性的影响。
用 1、2、3 和 4 位取代基取代蒽醌环的 6 个系列的新 AQ 衍生物进行了测试，发现了能够在低微摩尔范围内抑制 HIV-1 RT 相关 RNase H 活性的新类似物。
我们的结果表明，AQ 衍生物是很有前途的抗 RNase H 抑制剂。
