Relationships between the chemical structure and the biological properties of some eremophilane compounds related to PR toxin

Dacrymenone and VM 3298-2 - New Antibiotics with Antibacterial and Antifungal Activity

“…The greatly reduced biological activities of dacrymenone (1) are likely to be due to the lack of the aldehyde group and the two oxirane rings present in PR toxin. While no cytotoxic activities of dacrymenone (1) were observed at concentrations up to 100 µg/ml, sporogen A01 (4), a closely related eremophilane containing an additional oxirane ring is highly cytotoxic (IC 50 : 1Ð5 µg/ml) (Schneider et al, 1997). VM 3298-2 (2) is cytotoxic towards Colo-320, HL-60, and L1210 cells (see Fig.…”

“…2 exhibits weak antifungal activity against yeasts and filamentous fungi, with the highest activity on Candida parapsilosis at 25 µg/ml (110 µm) and Saccharomyces cerevisiae at 10 µg/ml (44 µm). The eremophilane PR Toxin (3) from Penicillium roquefortii was reported to exhibit strong cytotoxic, fungicidal and bactericidal properties (Moulé et al, 1977). The greatly reduced biological activities of dacrymenone (1) are likely to be due to the lack of the aldehyde group and the two oxirane rings present in PR toxin.…”

“…Up to now not much is known of their secondary metabolism and their products. In one of our previous screenings we isolated an antifungal compound from Dacrymyces stillatus which turned out to be identical to glykenin IV A, produced by an unclassified basidiomycete (Wunder, 1995;Nishida F. et al, 1991;Nishida F. et al, 1994). In the course of a screening for antibiotics against Candida species another strain of Dacrymyces was found to produce compounds not related to the glykenins.…”

Inhibition of protein synthesis by PR toxin, a mycotoxin from Penicillium roqueforti

“…The LDso for male rats and mice is about 7 mg/kg by intraperitoneal injection. PRT induces short-term alterations in liver metabolism [3][4][5]. In the experiments presented here, we studied the inhibition of protein synthesis by PRT in an attempt to elucidate the mechanism of this effect.…”

The structure and absolute configuration of PR toxin

“…The biological properties result particularly in the inhibition of protein and RNA synthesis (Moule, Jemmali & Rousseau, 1976). A study of the relationships between the chemical structure and the biological properties suggested the important role of an aldehyde group in position 12 associated with an epoxide group and an a, fl-unsaturated ketone (Moule, Moreau & Bousquet, 1977). In order to discover the action mechanism, it was important to determine the absolute configuration, * To whom correspondence should be addressed.…”