tetano
Editor, Senior Moderator
Bioorg Med Chem Lett. 2016 Feb 1;26(3):769-73. doi: 10.1016/j.bmcl.2015.12.100. Epub 2015 Dec 29.
[h=1]The semi-synthesis of novel andrographolide analogues and anti-influenza virus activity evaluation of their derivatives.[/h] Yuan L[SUP]1[/SUP], Zhang C[SUP]1[/SUP], Sun H[SUP]1[/SUP], Liu Q[SUP]1[/SUP], Huang J[SUP]1[/SUP], Sheng L[SUP]1[/SUP], Lin B[SUP]1[/SUP], Wang J[SUP]1[/SUP], Chen L[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Two novel andrographolide analogues with the structural motif of Δ(8,17)-alkene exo-to-endo isomerization, AI78 and AI89, were semi-synthesized firstly. Two series of derivatives were designed and synthesized based on the synthetic pathway (including series I: olefin isomerizing to endocyclic Δ(8,9) and series II: olefin isomerizing to endocyclic Δ(7,8)). The anti-influenza virus activity in vitro for all derivatives was evaluated. Among the compounds synthesized, compound 38 with benzyl amino group showed the greatest potency against H3N2 and was approximately 1.5-fold more potent than that of Lianbizhi, andrographolide analogue used clinically in China. Adamantyl derivative, 43, presented the lowest toxicity, with a higher TC50 and TI values than Lianbizhi. The structure-activity relationships studies of the synthetic analogues indicated that the endocyclic Δ(7,8)-double bond is preferable for anti-viral effect. Furthermore, the introduction of the fatty amino attached to the rigid skeleton at C-17 is beneficial for activity.
Copyright ? 2016 Elsevier Ltd. All rights reserved.
[h=4]KEYWORDS:[/h] Andrographolide; Anti-influenza virus activity; Semi-synthesis; Structure modification; Δ(8,17)-Alkene exo-to-endo isomerization
PMID: 26791013 [PubMed - in process]
[h=1]The semi-synthesis of novel andrographolide analogues and anti-influenza virus activity evaluation of their derivatives.[/h] Yuan L[SUP]1[/SUP], Zhang C[SUP]1[/SUP], Sun H[SUP]1[/SUP], Liu Q[SUP]1[/SUP], Huang J[SUP]1[/SUP], Sheng L[SUP]1[/SUP], Lin B[SUP]1[/SUP], Wang J[SUP]1[/SUP], Chen L[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Two novel andrographolide analogues with the structural motif of Δ(8,17)-alkene exo-to-endo isomerization, AI78 and AI89, were semi-synthesized firstly. Two series of derivatives were designed and synthesized based on the synthetic pathway (including series I: olefin isomerizing to endocyclic Δ(8,9) and series II: olefin isomerizing to endocyclic Δ(7,8)). The anti-influenza virus activity in vitro for all derivatives was evaluated. Among the compounds synthesized, compound 38 with benzyl amino group showed the greatest potency against H3N2 and was approximately 1.5-fold more potent than that of Lianbizhi, andrographolide analogue used clinically in China. Adamantyl derivative, 43, presented the lowest toxicity, with a higher TC50 and TI values than Lianbizhi. The structure-activity relationships studies of the synthetic analogues indicated that the endocyclic Δ(7,8)-double bond is preferable for anti-viral effect. Furthermore, the introduction of the fatty amino attached to the rigid skeleton at C-17 is beneficial for activity.
Copyright ? 2016 Elsevier Ltd. All rights reserved.
[h=4]KEYWORDS:[/h] Andrographolide; Anti-influenza virus activity; Semi-synthesis; Structure modification; Δ(8,17)-Alkene exo-to-endo isomerization
PMID: 26791013 [PubMed - in process]