Desideri N, Sestili I, Stein M L, Tramontano E, Corrias S, La Colla P
Dipartimento di Studi Farmaceutici, Università La Sapienza di Roma, Italy.
Antivir Chem Chemother. 1998 Nov;9(6):497-509. doi: 10.1177/095632029800900606.
A series of new hydroxybenzoic and hydroxycinnamic acid flavon-3-yl esters were synthesized in order to obtain compounds targeting the human immunodeficiency virus (HIV) type 1 integrase (IN). The esters were tested for anti-IN and anti-reverse transcriptase (RT) activity in enzyme assays and for anti-HIV-1, anti-proliferative and anti-topoisomerase activity in cell-based assays. In enzyme assays, the two gallic acid flavon-3-yl esters showed a notable IN inhibition (IC50 values were 8.3 and 9.1 microM, respectively), while the two caffeic acid flavon-3-yl esters exhibited a modest activity (IC50 75 and 60 microM, respectively). Replacement of hydroxyl groups resulted in loss of potency. Caffeic acid 3',4'-dichloroflavon-3-yl ester also inhibited the RT activity whereas it was not active on human topoisomerases. It therefore represents an interesting example of a compound specifically targeting more than one step of the virus replication cycle.
为了获得靶向人类免疫缺陷病毒1型整合酶（IN）的化合物，合成了一系列新的羟基苯甲酸和羟基肉桂酸黄酮-3-基酯。在酶分析中测试了这些酯的抗IN和抗逆转录酶（RT）活性，并在基于细胞的分析中测试了它们的抗HIV-1、抗增殖和抗拓扑异构酶活性。在酶分析中，两种没食子酸黄酮-3-基酯显示出显著的IN抑制作用（IC50值分别为8.3和9.1微摩尔），而两种咖啡酸黄酮-3-基酯表现出适度的活性（IC50分别为75和60微摩尔）。羟基的取代导致活性丧失。咖啡酸3',4'-二氯黄酮-3-基酯也抑制RT活性，而对人拓扑异构酶无活性。因此，它是一种特异性靶向病毒复制周期多个步骤的化合物的有趣例子。
