ABSTRACT
Nineteen carbazole alkaloids modified from heptaphylline (I) and 7-methoxyheptaphylline (II) isolated from Clausena harmandiana were synthesized. Among these derivatives, Ih and IIi showed cytotoxicity against the NCI-H187 cell line with IC(50) values of 0.02 and 0.66 µM, respectively, which are about 138 and 4 fold stronger than the ellipticine standard. In addition, oxime Ih displayed cytotoxicity against KB cells with an IC(50) value of 0.17 µM which is about 10 times stronger than the ellipticine. This compound demonstrated weak cytotoxicity against Vero cells (IC(50) = 66.01 µM). The results show convincingly that Ih may be a promising lead for the development of cytotoxic agents.
Subject(s)
Carbazoles/chemical synthesis , Carbazoles/pharmacology , Animals , Cell Line, Tumor , Chlorocebus aethiops , Drug Screening Assays, Antitumor , Humans , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Mass Spectrometry , Spectroscopy, Fourier Transform Infrared , Vero CellsABSTRACT
Four new carbazole alkaloids, claurailas A-D (1-4), as well as 12 known carbazoles and three known coumarins were isolated from the roots of Clausena harmandiana. Heptaphylline (6) and 7-methoxyheptaphylline (7) showed strong cytotoxicity against NCI-H187 and KB cell lines with IC(50) values ranging from 1.3 to 2.7 µM. Compound 7 showed no cytotoxicity against Vero cells.
Subject(s)
Alkaloids/isolation & purification , Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Carbazoles/isolation & purification , Carbazoles/pharmacology , Clausena/chemistry , Coumarins/isolation & purification , Alkaloids/chemistry , Animals , Antineoplastic Agents, Phytogenic/chemistry , Carbazoles/chemistry , Chlorocebus aethiops , Coumarins/chemistry , Coumarins/pharmacology , Drug Screening Assays, Antitumor , Humans , Inhibitory Concentration 50 , KB Cells , Plant Roots/chemistryABSTRACT
Two carbazoles (compounds 1 and 2) and one coumarin (compound 8) from Clausena harmandiana exhibited significant glucose uptake activity in L6 myotubes in a time and dose dependent manner. In addition, compounds 2 and 8 were inhibited by p38 mitogen-activated protein kinases and phosphatidylinositol 3-kinases, respectively.
Subject(s)
Carbazoles/pharmacology , Coumarins/pharmacology , Muscle Fibers, Skeletal/metabolism , Cell Survival/drug effects , Cells, Cultured , Clausena/chemistry , Cycloheximide/pharmacology , Cytochalasin B/pharmacology , Deoxyglucose/metabolism , Humans , Imidazoles/pharmacology , Muscle Fibers, Skeletal/drug effects , Plant Extracts/pharmacology , Plant Roots/chemistry , Pyridines/pharmacology , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitorsABSTRACT
The activity guided fractionation of the Clausena harmandiana root extracts led to the isolation of a coumarin, a ferulate, and eight carbazoles. This is the first report of the isolation of compounds 2-4 and 6-10 from this species, and this is the first time 10 was isolated from this genus. Compound 4 showed strong cytotoxicity against NCI-H187 cells with an IC(50) value of 1.63 microg/mL. Compound 5 demonstrated strong cytotoxicity against MCF-7 and KB cell lines with IC50 values of 2.21 and 1.74 microg/mL, respectively. Compounds 3 and 4 exhibited moderate cytotoxicity against the MCF-7 cell line, and 8 showed moderate cytotoxicity against NCIH187 and KB cell lines. Compounds 3 and 5 showed antiplasmodial activity with IC(50) values of 3.27 and 2.94 microg/mL, respectively.
