In vitro effect of fungal cyclodepsipeptides on leukemic cells: study of destruxins A, B and E

Abstract

The activities of three mycotoxins isolated from the hyphomycete Metarhizium anisopliae: destruxin A, B, and E (DA, DB and DE) are described and compared in vitro on leukemic cells. Their antitumor effect was investigated by flow cytometry on growth, cell viability and cell cycle perturbation 48 h after destruxin exposure. Against P388 leukemic cells, DE displayed greater antiproliferative activity than DA and DB. The minimum concentration required to inhibit 50% of cell proliferation is 0.33 microgram/ml for DE, 11.7 micrograms/ml for DA and 9.4 micrograms/ml for DB. Cell cycle modifications were only observed with DE at 50 and 10 micrograms/ml and consisted in an accumulation of the cells in G0/1 phase. DA and DB did not modify the number of cells in G0/1 of the cell cycle. Nevertheless a decrease in the number of cells in G2+M phase was induced by the three destruxins.

Impact of ring size on the copper(II) coordination abilities of cyclic tetrapeptides

“…Cyclopeptides play a variety of roles in living organisms; indeed they may act as hormones, toxins, antibiotics, molecules with enzymatic functions or as carrier molecules [1][2][3][4]. The most known is valinomicin, cyclopeptide is able of binding the alkali metal ions and transporting them through the biological membranes [1].…”

In vitro Synthesis of New Cyclodepsipeptides of the PF1022‐Type: Probing the α‐D‐Hydroxy Acid Tolerance of PF1022 Synthetase

“…This enantioselectivity is paralleled by ESYN, [18] and as a consequence with regard to enantioselectivity, homologous a-hydroxy acid recognition sites can be A C H T U N G T R E N N U N G assumed for this structural motif. Halogenated lactates, which are represented by 3-chloro-, 3-fluoro-and 3-bromolactate (compounds 2, 3 and 4, respectively) all show an increased A C H T U N G T R E N N U N G activity (174, 166 and 121 %, respectively) compared to lactate (1).…”

“…Cyclodepsipeptides (CDPs) represent an important category of natural peptide products that are characterised by the occurrence of at least one ester linkage. The great interest that this class of natural products has elicited is explained by the broad range of biological activities, including antitumour (destruxins A, B and E), [1] antibacterial (ramoplanin), antifungal (W493A and B), [2] insecticidal (verticillide) [3] or anthelmintic activities (PF1022A). [4] Helminths, including parasitic nematodes, cause significant health problems in both humans and animals and thus are a cause of diseases such as epileptic seizure and allergic shock or even onchocerciasis.…”

A New Destruxin as Inhibitor of Vacuolar-Type H+-ATPase ofSaccharomyces cerevisiae

“…[10] In addition to their insecticidal and phytotoxic activities, they were demonstrated to show antitumor [11] and antiviral [12] activities. Muroi et al [13] described destruxin B (3) as a specifically and dose-dependent inhibitor of vacuolar-type ATPase.…”