RP-1551s, a Family of Azaphilones Produced by Penicillium sp., Inhibit the Binding of PDGF to the Extracellular Domain of Its Receptor

Abstract

Nine azaphilones designated RP-1551-1, -2, -3, -4, -5, -6, -7, -M1, and -M2 were isolated from the culture broth of Penicillium sp. SPC-21609 as inhibitors of PDGF binding to its receptor. RP-1551s inhibit the binding of PDGF AA to the extracellular domain of PDGF α-receptor with IC₅₀ values ranging from 0.1 to 2μM without affecting PDGF BB binding to the extracellular domain of PDGF β-receptor. PDGF binding was not restored after the PDGF α-receptor extracellular domain was washed in an attempt to remove the RP-1551-1 bound to the receptor. This result suggests that RP-1551-1 may irreversibly interact with the PDGF α-receptor. Since many azaphilone compounds possess high reactivity with an aminol group, RP-1551-1 may prevent PDGF AA binding by reacting with amino groups on the α-receptor extracellular domain.