Identification and synthesis of quinolizidines with anti-influenza a virus activity
- ACS Med Chem Lett. 2014 Jun 30;5(8):942-6. doi: 10.1021/ml500236n.
- 1. Surgical Science, Department of Surgery, Duke University Medical Center , Durham, North Carolina 27710, United States.
- 2. School of Dentistry, Meharry Medical College , Nashville, Tennessee 37208, United States.
- 3. Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina , Chapel Hill, North Carolina 27599, United States ; Chinese Medicine Research and Development Center, China Medical University and Hospital , Taichung, Taiwan.
Influenza A virus Infection causes a contagious respiratory illness that poses a threat to human health. However, there are limited anti-influenza A therapeutics available, which is further compounded by the emergence of drug resistant viruses. In this study, Sophora Quinolizidine Alkaloids were identified as a new class of anti-influenza A virus agents. Among the tested Sophora Alkaloids, dihydroaloperine exhibited the most potent activity with an EC50 of 11.2 μM. The potency of the Quinolizidine Alkaloids was improved by approximately 5-fold with chemical modifications on the aloperine molecule. These compounds were effective against an H1N1 influenza A virus that was resistant to the two antiflu drugs oseltamivir and amantadine. The identification of the Quinolizidine Alkaloids as effective and novel anti-influenza A agents may aid in the development of new therapeutics.