Structure and absolute stereochemistry of hectochlorin, a potent stimulator of actin assembly.
Hectochlorin (1) was isolated from marine isolates of Lyngbya majuscula collected from Hector Bay, Jamaica, and Boca del Drago Beach, Bocas del Toro, Panama. The planar structure was deduced by one- and two-dimensional NMR spectroscopy. X-ray crystallography was used to determine the absolute stereochemistry of hectochlorin as 2S,3S,14S,22S. Hectochlorin is equipotent to jasplakinolide (5) in its ability to promote actin polymerization, but unlike jasplakinolide, is unable to displace a fluorescent phalloidin analogue from polymerized actin. In addition, hectochlorin shows both a unique profile of cytotoxicity by the COMPARE algorithm and potent inhibitory activity toward the fungus Candida albicans. Structurally, hectochlorin resembles dolabellin and the recently reported lyngbyabellin class of compounds.
Marquez
Brian L
BL
College of Pharmacy, Oregon State University, Corvallis, Oregon 97331, USA.
Watts
Karl Shawn
KS
Yokochi
Alexandre
A
Roberts
Mary Ann
MA
Verdier-Pinard
Pascal
P
Jimenez
Jorge I
JI
Hamel
Ernest
E
Scheuer
Paul J
PJ
Gerwick
William H
WH
D000199:Actins / Q000187:drug effects* / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D018360:Crystallography, X-Ray; D000458:Cyanobacteria / Q000737:chemistry*; D047630:Depsipeptides; D016650:Fluorescein-5-isothiocyanate; D020128:Inhibitory Concentration 50; D007563:Jamaica; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008235:Lyngbya Toxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010176:Panama; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013844:Thiazoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
D000199:Actins; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D047630:Depsipeptides; D007783:Lactones; D008235:Lyngbya Toxins; D010456:Peptides, Cyclic; D013844:Thiazoles; C454807:hectochlorin; C410925:lyngbyabellin A; C416586:lyngbyabellin B; C057531:jasplakinolide; D016650:Fluorescein-5-isothiocyanate