Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
Pharmacy Program, Pharmacology Stream, Allied Health Department, College of Health Sciences, University of Bahrain, P.O. Box 32038, Kingdom of Bahrain.
Future Med Chem. 2018 Oct 1;10(19):2325-2344. doi: 10.4155/fmc-2018-0058. Epub 2018 Sep 14.
AIM: Novel open chain and cyclized derivatives containing pyrazole scaffold were designed, synthesized and evaluated as antileishmanial compounds. Methodology & results: In silico reverse docking experiment suggested Leishmania major pteridine reductase (Lm-PTR1) as a putative target for the synthesized compounds. In vitro antileishmanial screening against L. major promastigotes and amastigotes using miltefosine and amphotericin B as references showed that the majority of the compounds displayed activity higher than miltefosine. Compounds 3i and 5 showed the highest antileishmanial activity with IC values of 1.45 ± 0.08 μM and 2.30 ± 0.09 μM, respectively, for the amastigote form. In silico drug-likeness and toxicity predictions showed acceptable profiles for most of the compounds, which were validated by experimental toxicity studies. CONCLUSION: This study offers promising entities for antileishmanial activity.
目的：设计、合成并评估含有吡唑骨架的新型开链和环化衍生物，作为抗利什曼原虫化合物。
方法与结果：计算机反向对接实验表明，利什曼原虫蝶呤还原酶（Lm-PTR1）可能是合成化合物的靶标。以米替福新和两性霉素 B 为参照，对利什曼原虫前鞭毛体和无鞭毛体进行体外抗利什曼原虫筛选，结果表明，大多数化合物的活性均高于米替福新。化合物 3i 和 5 对无鞭毛体的抗利什曼原虫活性最高，IC 值分别为 1.45 ± 0.08 μM 和 2.30 ± 0.09 μM。计算机药物相似性和毒性预测显示，大多数化合物具有可接受的特性，这通过实验毒性研究得到了验证。
结论：该研究提供了具有抗利什曼原虫活性的有前途的实体。
Pharmaceuticals (Basel). 2022-3-7
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