A cyclodepsipeptide with anthelmintic activity
PF1022A is a novel anthelmintic cyclodepsipeptide. It was isolated from cultured mycelia of PF1022 Mycelia Sterilia, and exhibited strong anthelmintic activities against Ascaridia galli in chickens. [2] PF1022A seems to be a safe alternative to other anthelmintic drugs [1].
PF1022 is consisted of four alternating residues of N-methyl-L-leucine and four residues of D-phenyl-lactate or D-lactate [3]. PF1022A binds to the latrophilin-like transmembrane receptor and is important for pharyngeal pumping in nematodes. Furthermore, PF1022A binds to GABA receptors, which might contribute to the anthelmintic effect. PF1022A acts as an ionophore. In necrotic cells, PF1022A did not induce cell death indicated by lack of cellular lactate dehydrogenase release. PF1022A-induced cytotoxicity is impacted on the cell cycle and apoptosis regulating proteins p53, bax and p21, but not Bcl-2.
The efficacy of?PF 1022A?was investigated against the following parasite species: Strongyloides ratti and Nippostrongylus brasiliensis in rats, Ancylostoma caninum in dogs, Trichostrongylus colubriformis and Haemonchus contortus in sheep, small strongyles (cyathostomes) in horses, and Dictyocaulus viviparus in cattle. Oral, subcutaneous or intravenous application at doses varied from 1 to 10 mg/kg body weight was compared in livestock animals. High degrees of efficacy were found in all the above-cited examinations, and no clinical signs of impatience were observed. [4]
参考文献:
[1].Dornetshuber R, Kamyar MR, Rawnduzi P et al.? Effects of the anthelmintic drug PF1022A on mammalian tissue and cells. Biochem Pharmacol. 2009 Apr 15;77(8):1437-44.
[2].Sasaki T, Takagi M, Yaguchi T et al.? A new anthelmintic cyclodepsipeptide, PF1022A. J Antibiot (Tokyo). 1992 May;45(5):692-7.
[3].Yanai K, Sumida N, Okakura K et al.? Para-position derivatives of fungal anthelmintic cyclodepsipeptides engineered with Streptomyces venezuelae antibiotic biosynthetic genes. Nat Biotechnol. 2004 Jul;22(7):848-55. Epub 2004 Jun 6.
[4].Von Samson-Himmelstjerna G, Harder A, Schnieder T.? In vivo activities of the new anthelmintic depsipeptide PF 1022A. Parasitol Res. 2000 Mar;86(3):194-9.
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