An inhibitor of CCL2-induced chemotaxis from the fungus Leptoxyphium sp.
A biological screen used to identify inhibitors of monocyte chemotactic protein-1 (CCL2)-induced chemotaxis was applied in the activity-guided fractionation of an extract from a fungus of the genus Leptoxyphium sp. Inhibition of CCL2-induced chemotaxis was traced to a new dichlorinated diketopiperazine, cyclo(13,15-dichloro-L-Pro-L-Tyr). A structure-activity relationship (SAR) study evaluating relative activities of cyclo(13,15-dichloro-L-Pro-L-Tyr) and a nonchlorinated homologue cyclo(L-Pro-L-Tyr) showed that the dichlorinated molecule was 10- to 20-fold more active than the nonchlorinated form, while no activity was observed for cyclo(D-N-methylLeu-L-Trp).
Klausmeyer
Paul
P
Natural Products Support Group, SAIC-Frederick, Inc., Frederick, Maryland 21702, USA.
Howard
O M Zack
OM
Shipley
Suzanne M
SM
McCloud
Thomas G
TG
D001203:Ascomycota / Q000737:chemistry*; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors*; D004151:Dipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D029791:Ericaceae / Q000382:microbiology; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D018932:Chemokine CCL2; D004151:Dipeptides; D010456:Peptides, Cyclic; C543357:cyclo(13,15-dichloro-L-Pro-L-Tyr)