Dual inhibitors of the dengue and West Nile virus NS2B-NS3 proteases: Synthesis, biological evaluation and docking studies of novel peptide-hybrids.
Dual inhibitors of the dengue and West Nile virus NS2B-NS3 proteases: Synthesis, biological evaluation and docking studies of novel peptide-hybrids.
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登革热和西尼罗河病毒 NS2B-NS3 蛋白酶的双重抑制剂：新型肽杂种的合成、生物学评价和对接研究。
DOI：
10.1016/j.bmc.2015.07.012
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发表时间：
2015
影响因子：
3.5
通讯作者：
C. Klein
中科院分区：
文献类型：
--
作者：
Allan Bastos Lima;Mira A. M. Behnam;Yasmin El Sherif;Christoph Nitsche;S. M. Vechi;C. Klein
登革热病毒（DENV）和西尼罗河病毒（WNV）是蚊媒虫媒病毒，可导致人类急性全身性疾病和严重健康状况。发现能够预防感染或治疗受感染个体的疗法仍然是一项重大挑战，因为迄今尚未开发出疫苗或特定的有效治疗方法。在此背景下，我们介绍了基于非极性基团2,4-噻唑烷二酮支架的新型多肽杂合体的合成、表征、生物学评价和对接研究。最有希望的化合物对WNV蛋白酶的ic50为0.75 μM，与我们之前报道的化合物相比，活性提高了70倍。实验结果和对接研究与支架中的非极性基团对于抑制剂与DENV和WNV NS2B-NS3丝氨酸蛋白酶底物识别区疏水口袋之间的相互作用很重要的假设一致。
Dengue virus (DENV) and West Nile virus (WNV) are mosquito-borne arboviruses responsible for causing acute systemic diseases and severe health conditions in humans. The discovery of therapies capable to prevent infections or treat infected individuals remains an important challenge, since no vaccine or specific efficient treatment could be developed so far. In this context, we present herein the synthesis, characterization, biological evaluation and docking studies of novel peptide-hybrids based on 2,4-thiazolidinedione scaffolds containing non-polar groups. The most promising compound has an IC50of 0.75 μM against WNV protease, which represents a seventyfold improvement in activity compared to our previously reported compounds. Experimental results and docking studies are in agreement with the hypothesis that a non-polar group in the scaffold is important to obtain interactions between the inhibitors and a hydrophobic pocket in the substrate recognition region of the DENV and WNV NS2B–NS3 serine proteases.
影响因子：
4.8
作者：
Tyler KL
通讯作者：
Tyler KL