Comparative analysis of curcumin analogues on anti-influenza virus activity
| Autor: | Jun-Lin Ou, 歐俊麟 |
|---|---|
| Rok vydání: | 2013 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 101 Curcumin is a commonly used colouring agent and spice in food. Accumulated evidence indicates that curcumin is associated with a great variety of pharmacological activities, including an antimicrobial effect. Previously, we reported curcumin inhibits the infection of type A influenza virus (IAV) and proved one of the mechanisms is through interfering the viral HA activity. To investigate the structure contributing to its anti-IAV activity, structural and functional analogues of Curcumin (Cur), such as Tetrahydrocurcumin (THC), Monoacetylcurcumin (MAC) and Petasiphenol (Pet) were comparatively analyzed in the current study. The result of time-of-drug addition tests revealed that all the analogues analyzed were able to inhibit IAV production in cell cultures; MAC has a similar strength to curcumin, whereas Pet and THC inhibit IAV to a much less extent than curcumin. Comparative analysis of curcumin analogues described herein demonstrated that Thc and Pet have much less effect on suppression of plaque formation ability; the EC50 of pet are 14.65 μM, whereas curcumin and MAC is 0.17 and 0.2 μM, respectively. Surprisingly, none of the analogues harbors HA inhibition effect. Considering that as with curcumin, the structure of MAC contains two double bonds in the central seven-carbon chain, whereas Pet and THC has one or none, respectively, it indicates the presence of double bond is crucial for the anti-IAV activity. The unsaturated carbonyl group acts as the acceptor of Michael addition reaction that involves in the intermolecular conjugation by formation of covalent Michael adducts with certain proteins. It is very possible that via Michael addition reaction, curcumin conjugated with viral protein that in turns alters or interferes with the function of viral surface proteins and inactivate virus infectivity. In conclusion, THC, one of the stable curcumin metabolites exhibits anti-IAV activity and MAC appears to be an effective agent for inhibition of IAV infection. Moreover, comparative analysis of curcuminoids indicated that the two double bonds in the central seven-carbon chain contribute to the curcumin -mediated anti-IAV activity. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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