The marine sponge Diacarnus bismarckensis as a source of peroxiterpene inhibitors of Trypanosoma brucei, the causative agent of sleeping sickness.
Human African trypanosomiasis, also known as African sleeping sickness, is a neglected tropical disease with inadequate therapeutic options. We have launched a collaborative new lead discovery venture using our repository of extracts and natural product compounds as input into our growth inhibition primary screen against Trypanosoma brucei. Careful evaluation of the spectral data of the natural products and derivatives allowed for the elucidation of the absolute configuration (using the modified Mosher's method) of two new peroxiterpenes: (+)-muqubilone B (1a) and (-)-ent-muqubilone (3a). Five known compounds were also isolated: (+)-sigmosceptrellin A (4a), (+)-sigmosceptrellin A methyl ester (4b), (-)-sigmosceptrellin B (5), (+)-epi-muqubillin A (6), and (-)-epi-nuapapuin B methyl ester (7). The isolated peroxiterpenes demonstrated activities in the range IC(50) = 0.2-2 mug/mL.
Rubio
Brent K
BK
Department of Chemistry and Biochemistry and Institute for Marine Sciences, University of California Santa Cruz, Santa Cruz, California 95064, USA.
Tenney
Karen
K
Ang
Kean-Hooi
KH
Abdulla
Maha
M
Arkin
Michelle
M
McKerrow
James H
JH
Crews
Phillip
P
D000818:Animals; D006801:Humans; D008386:Marine Biology; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010545:Peroxides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D011161:Porifera / Q000737:chemistry*; D013237:Stereoisomerism; D013729:Terpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000209:etiology
D010545:Peroxides; D013729:Terpenes