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

Marine Drugs

Mårten Strand³  Marcus Carlsson²  Hanna Uvell²  Koushikul Islam³  Karin Edlund³  Inger Cullman²  Björn Altermark¹  Ya-Fang Mei³  Mikael Elofsson²  Nils-Peder Willassen¹  Göran Wadell³ 

[1] Department of Chemistry, Faculty of Science and Technology, University of Tromsø, Tromsø 9037, Norway; E-Mails:;Laboratories for Chemical Biology, Department of Chemistry, Umeå University, Umeå SE-90187, Sweden; E-Mails:;Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå SE-90185, Sweden; E-Mails:

关键词: adenovirus;    antiviral;    natural products;    secondary metabolites;    marine actinobacteria;    extract screening;    butenolides;   

DOI  :  10.3390/md12020799

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.