ABSTRACT
A series of 49 oxygenated tricyclic carbazole derivatives has been tested for inhibition of the growth of Mycobacterium tuberculosis and a mammalian cell line (vero cells). From this series, twelve carbazoles showed a significant anti-TB activity. The four most active compounds were the naturally occurring carbazole alkaloids clauszoline-M (45), murrayaline-C (41), carbalexin-C (27), and the synthetic carbazole derivative 22 with MIC90 values ranging from 1.5 to 3.7µM. The active compounds were virtually nontoxic for the mammalian cell line in the concentration range up to 50µM.
Subject(s)
Alkaloids/chemistry , Antitubercular Agents/chemistry , Carbazoles/chemistry , Alkaloids/chemical synthesis , Alkaloids/pharmacology , Animals , Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Carbazoles/chemical synthesis , Carbazoles/pharmacology , Cell Survival/drug effects , Chlorocebus aethiops , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects , Structure-Activity Relationship , Vero CellsABSTRACT
Pd(II) caught in the act: The diaryl Pd(II) intermediate of a Pd(II)-catalyzed oxidative biaryl bond formation proceeding via a double C-H bond activation has been isolated and fully characterized, including an X-ray crystal structure analysis. Stabilization due to chelation by adjacent pivaloyloxy and acetyl groups has allowed the isolation of this long-sought crucial intermediate. On gentle warming, the complex is transformed into a carbazole product, and the catalytically active Pd(II) species is regenerated by oxidation with Cu(II).
