Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, Italy.
Dipartimento di Scienze della Salute, Università Magna Graecia di Catanzaro, Campus 'S. Venuta', Viale Europa, 88100 Catanzaro, Italy.
Molecules. 2021 Jun 23;26(13):3821. doi: 10.3390/molecules26133821.
Current therapeutic protocols for the treatment of HIV infection consist of the combination of diverse anti-retroviral drugs in order to reduce the selection of resistant mutants and to allow for the use of lower doses of each single agent to reduce toxicity. However, avoiding drugs interactions and patient compliance are issues not fully accomplished so far. Pursuing on our investigation on potential anti HIV multi-target agents we have designed and synthesized a small library of biphenylhydrazo 4-arylthiazoles derivatives and evaluated to investigate the ability of the new derivatives to simultaneously inhibit both associated functions of HIV reverse transcriptase. All compounds were active towards the two functions, although at different concentrations. The substitution pattern on the biphenyl moiety appears relevant to determine the activity. In particular, compound 2-{3-[(2-{4-[4-(hydroxynitroso)phenyl]-1,3-thiazol-2-yl} hydrazin-1-ylidene) methyl]-4-methoxyphenyl} benzamide bromide () was the most potent towards RNaseH (IC = 4.5 mM)- and RDDP (IC = 8.0 mM) HIV RT-associated functions.
目前治疗 HIV 感染的治疗方案包括联合使用多种抗逆转录病毒药物，以减少耐药突变体的选择，并允许使用每种单一药物的较低剂量，以降低毒性。然而，避免药物相互作用和患者依从性仍然是目前尚未完全解决的问题。在我们对潜在的抗 HIV 多靶点药物的研究中，我们设计并合成了一个联苯腙 4-芳基噻唑衍生物的小文库，并对其进行了评估，以研究新衍生物同时抑制 HIV 逆转录酶两种相关功能的能力。所有化合物对这两种功能都有活性，尽管浓度不同。联苯部分的取代模式似乎与确定活性有关。特别是，化合物 2-{3-[(2-{4-[4-(羟基亚硝酰基)苯基]-1,3-噻唑-2-基}肼-1-亚基)甲基]-4-甲氧基苯基}苯甲酰胺溴化物（）对 RNaseH（IC = 4.5 mM）和 RDDP（IC = 8.0 mM）HIV RT 相关功能的活性最强。
