Alfadhli Ayna, Mack Andrew, Harper Logan, Berk Sam, Ritchie Christopher, Barklis Eric
Oregon Health & Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States.
Oregon Health & Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States.
Bioorg Med Chem. 2016 Nov 1;24(21):5618-5625. doi: 10.1016/j.bmc.2016.09.028. Epub 2016 Sep 12.
We have analyzed a set of quinolinequinones with respect to their reactivities, cytotoxicities, and anti-HIV-1 properties. Most of the quinolinequinones were reactive with glutathione, and several acted as sulfhydryl crosslinking agents. Quinolinequinones inhibited binding of the HIV-1 matrix protein to RNA to varying degrees, and several quinolinequinones showed the capacity to crosslink HIV-1 matrix proteins in vitro, and HIV-1 structural proteins in virus particles. Cytotoxicity assays yielded quinolinequinone CC values in the low micromolar range, reducing the potential therapeutic value of these compounds. However, one compound, 6,7-dichloro-5,8-quinolinequinone potently inactivated HIV-1, suggesting that quinolinequinones may prove useful in the preparation of inactivated virus vaccines or for other virucidal purposes.
我们已经分析了一组喹啉醌的反应活性、细胞毒性和抗HIV-1特性。大多数喹啉醌可与谷胱甘肽发生反应,有几种还可作为巯基交联剂。喹啉醌在不同程度上抑制HIV-1基质蛋白与RNA的结合,有几种喹啉醌在体外显示出交联HIV-1基质蛋白以及病毒颗粒中HIV-1结构蛋白的能力。细胞毒性试验得出喹啉醌的CC值在低微摩尔范围内,降低了这些化合物的潜在治疗价值。然而,一种化合物,即6,7-二氯-5,8-喹啉醌能有效灭活HIV-1,这表明喹啉醌可能在制备灭活病毒疫苗或用于其他杀病毒目的方面证明是有用的。