Study On The FR901464 Analogs From Pseudomonas And Cytotoxocity Activities Thereof

FR901464 and its analogs?FR901463 and FR901465?,a group of PKS-NRPS,mainly occur in the genus of Pseudomonas.These metabolites displayed strong inhibitory effects against a series of tumor cell lines with the IC₅₀ values of 0.3-3.4 nM.Different from clinical anti-cancer drugs,these compounds exerted their cytotoxicity by inhibiting the mRNA splicing.However,FR901464 and its analogues also show extremely strong toxic and side effects in clinical trials,which limited their application in clinic.In order to obtain metabolites with similar structures to FR901464 with good activity but low toxicity,the subject selected Pseudomonas sp.for the isolation of new FR901464 analogs.As a result,eight FR901464 analogs were isolated from the strain by chromatographic techniques.Seven compounds were determined by spectroscopic methods,including four new compounds and three known ones.Some isolates were tested for their cytotoxicity activity.The results showed that four compounds displayed potent cytotoxicity against A549 and MDA-MB-231,besides FR901464 and FR901463.The potency of compound 4 is 100-fold as that of positive control taxol against A549.This research offers new lead compounds for cancer treatment.