Mycolactone and related compounds, compositions and methods of use

摘要

The present invention provides, inter alia, polyketide macrolides including a polyketide macrolide of structure (2) wherein R<1>-R<5> are the same or different and each is independently selected from the group consisting of hydrogen, R<6>, a C(O)R<7>, a C(S)R<7>, a C(O)NHR<7>, and a C(S)NHR<7>, each occurrence of R<6> is independently selected from the group consisting of a C1-C6 alkyl, a C5-C12 aryl, and a sugar, each occurrence of R7 is independently selected from the group consisting of hydrogen, a C1-C6 alkyl, and a C5-C12 aryl, and wherein R<1> and R<2>, R<2> and R<3>, and/or R<4> and R<5> can be taken together to form a ketal ring. Also provided are asceptic mixtures of polyketide macrolides isolated from M. ulcerans in a pharmaceutically acceptable carrier, methods of using the polyketide macrolides and aseptic mixtures to inhibit cancer and suppress an inflammatory response in a mammal, a method of inducing an immune response to Mycobacteria ulcerans without inducing a buruli ulcer, and a composition comprising M. ulcerans.