Isolation and Characterization of Anti-Adenoviral Secondary Metabolites from Marine Actinobacteria

• Published in: Marine Drugs
• Main Authors: Mårten Strand, Marcus Carlsson, Hanna Uvell, Koushikul Islam, Karin Edlund, Inger Cullman, Björn Altermark, Ya-Fang Mei, Mikael Elofsson, Nils-Peder Willassen, Göran Wadell, Fredrik Almqvist
• Format: Text
• Language: English
• Published: Multidisciplinary Digital Publishing Institute 2014
• Subjects: adenovirus; antiviral; natural products; secondary metabolites; marine actinobacteria; extract screening; butenolides; Norway; Vestfjorden
• Online Access: https://doi.org/10.3390/md12020799

Adenovirus infections in immunocompromised patients are associated with high mortality rates. Currently, there are no effective anti-adenoviral therapies available. It is well known that actinobacteria can produce secondary metabolites that are attractive in drug discovery due to their structural diversity and their evolved interaction with biomolecules. Here, we have established an extract library derived from actinobacteria isolated from Vestfjorden, Norway, and performed a screening campaign to discover anti-adenoviral compounds. One extract with anti-adenoviral activity was found to contain a diastereomeric 1:1 mixture of the butenolide secondary alcohols 1a and 1b. By further cultivation and analysis, we could isolate 1a and 1b in different diastereomeric ratio. In addition, three more anti-adenoviral butenolides 2, 3 and 4 with differences in their side-chains were isolated. In this study, the anti-adenoviral activity of these compounds was characterized and substantial differences in the cytotoxic potential between the butenolide analogs were observed. The most potent butenolide analog 3 displayed an EC50 value of 91 μM and no prominent cytotoxicity at 2 mM. Furthermore, we propose a biosynthetic pathway for these compounds based on their relative time of appearance and structure.