Inhibition of c-fos Proto-oncogene Induction by Sch 52900 and Sch 52901, Novel Diketopiperazines Produced by Gliocladium sp.

Abstract

Sch 52900 (1) and Sch 52901 (2), two new inhibitors of c-fos proto-oncogene induction, have been isolated from the fermentation broth of the fungal culture (SCF-1 168), Gliocladium sp. Along with compounds 1 and 2, a known compound verticillin A (3) was also obtained from the culture. Structure elucidation of 1 and 2, accomplished by analysis of spectral data in comparison with the data of 3, revealed both 1 and 2 were found to be closely related to the verticillin family of diketopiperazines. All three compoundsprevented serum-stimulated transcription of the humanc-fos promoter, using afos/lac Z reporter gene assay, with IC50 values of 1.5, 18 and 0.5fM for 1, 2 and 3, respectively. Northern analysis revealed that exposure of cells to compound3 causes inhibition of both phorbol ester-induced c-fos induction and serum-induced JE induction in the absence of inhibiting RNAsynthesis, as measured by [3H]uridine incorporation. These results suggest that this class of compounds exerts antitumor activity by blocking a signal transduction pathway that is commonto and necessary for the induction of at least a subset of immediate early genes involved in cell proliferation.

Verticillin G, a New Antibacterial Compound from Bionectra byssicola

“…The epidithiodioxopiperazine compounds such as verticillins, leptosins and Sch52900 were known to have antibacterial and antitumor activity [3,5]. The antitumor activity of Sch52900 was known to be due to the inhibition of c-fos proto-oncogene induction [7]. The active moiety of the epidithiodioxopiperazines with strong anti-MRSA activity, however, have not been reported.…”

“…1). Compound 1 is a new derivative of dimeric epidithiodioxopiperazine compounds such as verticillins AϳF [3,4], leptosins AϳC, K, K 1 and K 2 [5,6], Sch52900 [7], chaetosin and chetracin A [8].…”

Isolation and Total Synthesis of Albu­peptins A–D: 11‐Residue Peptaibols from the Fungus Gliocladium album

“…These include polyterpenoids, [1][2][3] polyketide glycosides, [4,5] di-and triketopiperazines, [3,[6][7][8][9] a bisindole, [10] and peptaibols. [11,12] Peptaibols are a family of fungal peptides that consist of 5-21 amino acids, and are biosynthesized by nonribosomal peptide synthetases (NRPS).…”

Diketopiperazines from Marine Organisms

“…Recently, the interest in these compounds increased because of their significant bioactivities including plant-growth promotion [27], antimicrobial activity [28], quorum-sensing signalling [29] [30], antitumor activity [31], antiviral activity [31], and inhibition against aflatoxin production [32].…”