11-Deoxylandomycinone and landomycins X-Z, new cytotoxic angucyclin(on)es from a Streptomyces cyanogenus K62 mutant strain.
Four new angucyclin(on)es, 11-deoxylandomycinone (1) and landomycins X-Z (2-4) were isolated from the crude extract of Streptomyces cyanogenus K62 mutant strain, along with the recently reported landomycins S, T and V (5-7) and five other known compounds. The structures of the new compounds 1-4 were elucidated by 1D and 2D NMR studies along with HR-MS analyses. Unique about the structures is that the fourth sugar moiety (sugar D) in landomycins X-Z (2-4) was β-D-amicetose instead of β-D-olivose, usually found in this position. The new angucyclin(on)es were biologically evaluated in comparison with previously known congeners against a small panel of MCF-7 (estrogen responsive) and MDA 231 (estrogen refractory) breast cancer cell lines. 11-deoxylandomycinone (IC(50) 2.1 ± 0.3 and 1.2 ± 0.4 μM) and landomycin Y (IC(50) 1.0 ± 0.1 and 2.0 ± 0.1 μM) showed the highest cytotoxic potencies against both the cell lines.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA.
Khaled A
KA
Shaaban
Chris
C
Stamatkin
Chendil
C
Damodaran
Jürgen
J
Rohr
D000617:Aminoglycosides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D003837:Deoxy Sugars / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D019906:Nuclear Magnetic Resonance, Biomolecular; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
D000617:Aminoglycosides; D000970:Antineoplastic Agents; D003603:Cytotoxins; D003837:Deoxy Sugars