Location: Natural Products Utilization ResearchTitle: Inuloxins A-D and derivatives as antileishmanial agents: structure-activity relationship study) Author
Submitted to: Journal of Antibiotics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/1/2014
Publication Date: 4/30/2014
Citation: Avolio, F., Rimando, A.M., Cimmino, A., Andolfi, A., Jain, S., Tekwani, B.L., Evidente, A. 2014. Inuloxins A-D and derivatives as antileishmanial agents: structure-activity relationship study. Journal of Antibiotics. 67(8):597-601. Interpretive Summary: Inuloxins A-D and alpha-costic acid, compounds previously isolated from the plant Inula viscose, and synthetic derivatives of inuloxins A, C and D were tested for their activity against the leishmania parasite Leishmania donovani. Inuloxin A showed the greatest inhibition of the parasite, and was as effective as the control antibiotic pentamidine. Structure-activity analysis certain structural feature necessary for the activity. These compounds, specifically inuloxin A, shows potential as new antileishmanial drug leads.
Technical Abstract: Inuloxins A-D (1-4) and a-costic acid (5), the phytotoxic compounds previously isolated from Inula viscosa, as well as synthetic derivatives of inuloxin A (compounds 6-10), inuloxin C (compound 11) and inuloxin D (compound 12) were tested in vitro for their activity against Leishmania donovani, the protozoan parasite and causative agent for visceral leishmaniasis. Inuloxins A, C, and D demonstrated strong antileshmanial activity, with inuloxin A being the most active. Inuloxin A showed activity similar to pentamidine, the control antileshmanial drug. Structure-activity analysis indicates that the furanone ring with an exocyclic methylene group is an important structural feature for the antileshmanial activity. These compounds, specifically inuloxin A, shows potential as new antileishmanial drug leads.