Structure–activity relationship studies of 1-(1′-hydroxyalkyl)rupestonic acid methyl esters against influenza viruses. Issue 6 (15th March 2017)

• Record Type: Journal Article
• Authors: Li, Gen; Zhao, Jiang-Yu; Niu, Chao; Nie, Li-Fei; Dong, Chang-Zhi; Aisa, Haji Akber
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 6(2017)
• Page Start: 1484
• Page End: 1487
• Publication Date: 2017-03-15
• Subjects: Rupestonic acid -- Synthesis -- X-ray crystallographic analysis -- Anti-influenza viruses; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.06.011
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A series of 1-(1′-hydroxyalkyl)rupestonic acid methyl esters were synthesized via the condensation of methyl rupestonate with various aldehydes in the presence of LDA. This mixed aldol reaction was highly stereoselective and all the new compounds were elucidated by detailed NMR and MS analyses. The absolute configurations of the newly formed stereocenters were further confirmed by X-ray crystallographic analysis of3d, the results of which were found to be opposite to the prediction based on Zimmerman-Traxler's and Houk's models. All the compounds synthesized were then evaluated for their in vitro inhibitory activities against influenza A (H1N1 and H3N2) and B viruses. The data showed that3p displayed the highest activity against influenza A H1N1 (IC50 = 0.69 μg/mL) and H3N2 (IC50 = 0.69 μg/mL) viruses, which were even better than Ribavirin and Oseltmivir. On the other hand, both3c and3o were found to show comparable activities with the reference drugs in inhibiting both influenza A and B viruses. Further studies will focus on reducing the cytotoxicity of the hits reported in this work.