Enhanced anti-influenza agents conjugated with anti-inflammatory activity
Novel dual-targeted, bifunctional anti-influenza drugs formed by conjugation with anti-inflammatory agents are disclosed. Exemplary drugs according to the invention include caffeic acid (CA)-bearing zanamivir (ZA) conjugates ZA-7-CA (1), ZA-7-CA-amide (7) and ZA-7-Nap (43) for simultaneous inhibition of influenza virus neuraminidase and suppression of proinflammatory cytokines. Synthetic methods for preparation of these enhanced anti-influenza conjugate drugs are provided. The synthetic bifunctional ZA conjugates act synergistically towards protection of mice lethally infected by H1N1 or H5N1 influenza viruses. The efficacy of ZA-7-CA, ZA-7-CA-amide and ZA-7-Nap conjugates is much greater than the combination therapy of ZA with anti-inflammatory agents.
1. A dual anti-influenza and anti-inflammatory compound selected from the group consisting of:
2. A dual-active pharmaceutical composition for simultaneously inhibiting influenza virus and inflammation, the composition comprising:
a compound of claim 1 ,
or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable excipient.
3. The pharmaceutical composition of claim 2 , wherein the compound inhibits both human and avian influenza virus.
4. The pharmaceutical composition of claim 2 , wherein the compound inhibits at least one of H1N1 and H5N1 strains of influenza virus.
5. A method for treating influenza infection in a subject, the method comprising: administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 2 .
6. The method of claim 5 , wherein the subject has, is suspected of having, or is at risk for influenza virus infection.