基于吡啶并[2,3-d]嘧啶和二氢吡啶并嘧啶化合物的多功能抗感染特性。
Versatile anti-infective properties of pyrido- and dihydropyrido[2,3-d]pyrimidine-based compounds.
机构信息
Department of Biology, College of Science and Arts, Qassim University, Unaizah 51911, Saudi Arabia; Department of Science Laboratories, College of Science and Arts, Qassim University, Ar Rass 51921, Saudi Arabia.
Laboratorio di Virologia Molecolare, Dipartimento di Scienze della Vita e Dell'Ambiente, Universitá degli Studi di Cagliari, Cittadella Universitaria di Monserrato SS554, 09042 Monserrato, Italy.
出版信息
Bioorg Med Chem. 2023 Jul 15;90:117376. doi: 10.1016/j.bmc.2023.117376. Epub 2023 Jun 15.
A series of 1H-indeno[2',1':5,6]dihydropyrido[2,3-d]pyrimidine and 1H-indeno[2',1':5,6]pyrido[2,3-d]pyrimidine derivatives was prepared and screened for antiparasitic and viral RNase H inhibitory activity. Several compounds showed considerable activity against Toxoplasma gondii parasites and Leishmania major amastigotes, which warrants further investigation. Based on the structural similarities of certain derivatives with common viral RNase H inhibitors, a HIV-1 RNase H assay was used to study the RNase H inhibition by selected test compounds. Docking of active derivatives into the active site of the HIV-1 RNase H enzyme was carried out. The new compound 2a, inactive in the antiparasitic tests, showed distinct HIV-1 RNase H inhibition. Thus, ring substitution determines antiparasitic or HIV-1 RNase H inhibitory activity of this promising compound class.
一系列 1H-茚并[2',1':5,6]二氢吡啶并[2,3-d]嘧啶和 1H-茚并[2',1':5,6]吡啶并[2,3-d]嘧啶衍生物被制备并筛选其抗寄生虫和病毒 RNA 酶 H 抑制活性。一些化合物对弓形虫寄生虫和利什曼原虫无鞭毛体表现出相当大的活性，这值得进一步研究。基于某些衍生物与常见病毒 RNA 酶 H 抑制剂的结构相似性，使用 HIV-1 RNA 酶 H 测定法研究了选定测试化合物对 RNA 酶 H 的抑制作用。将活性衍生物对接入 HIV-1 RNA 酶 H 酶的活性位点。在抗寄生虫试验中无活性的新化合物 2a 表现出明显的 HIV-1 RNA 酶 H 抑制作用。因此，环取代决定了该类有前途的化合物的抗寄生虫或 HIV-1 RNA 酶 H 抑制活性。
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