Bafilomycins produced in culture by Streptomyces spp. isolated from marine habitats are potent inhibitors of autophagy.
Five new bafilomycins, F (1) to J (5), have been isolated from laboratory cultures of two Streptomyces spp. obtained from marine sediments collected in British Columbia, and their structures have been elucidated by detailed analysis of spectroscopic data and the synthesis of model compounds. The new bafilomycins F (1), G (2), H (3), and J (5) along with several co-occurring known analogues showed potent inhibition of autophagy in microscopy and biochemical assays. The thiomorpholinone fragment present in bafilomycin F (1) has not previously been found in a natural product.
Carr
Gavin
G
Department of Chemistry, University of British Columbia, Vancouver, B.C., Canada.
Williams
David E
DE
Díaz-Marrero
Ana R
AR
Patrick
Brian O
BO
Bottriell
Helen
H
Balgi
Aruna D
AD
Donohue
Elizabeth
E
Roberge
Michel
M
Andersen
Raymond J
RJ
D001343:Autophagy / Q000187:drug effects*; D001955:British Columbia; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008386:Marine Biology; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry*
D018942:Macrolides