Synthesis and cytotoxic effects of deoxy-tomentellin

Cannabigerol (1, CBG), methyl 4-[(2E)-3,7-dimethyl-2,6-octadienyl)oxy]-3-me thoxybenzoate (2, DTM), 5-fluorouracil (3, FU) as a reference, and cannabid iol (4, CBD) were tested for their growth inhibitory effects against KB(ATC C NO, OCL 17) cell lines using two different assays, the 3-(4,5-dimethylthi azol-2-yl)-2,5-diphenyl-2H-tetrazoliumbromide (MTT) assay and the sulforhod -amine B protein (SRB) assay. These compounds showed inhibitory activity in vitro in the micromolar range against KB cell lines. In general, the antit umor activities of these compounds (1, 2, 3 and 4) were dose-dependent over the micromolar concentration range of 1 to 100 M. The comparison of IC50 v alues of these compounds in tumor cell lines showed that their susceptibili ty to these compounds decreases in the following order: DTM > CBD > 5-FU > CBG by MTT assay and DTM = CBD > 5-FU > CBG by SRB assay. CBC 1, DTM 2, 5-F U 3, and CBD 4 were tested for their cytotoxic effects on NIH 3T3 fibroblas ts using two different assays, the MTT assay and SRB assay. These compounds exhibited potent cytotoxic activities in vitro in the micromolar range aga inst NIH 3T3 fibroblasts. In general, the cytotoxic activities of these com pounds (1, 2, 3 and 4) were dose-dependent over the micromolar concentratio n range of 1 to 100 M. The comparison of CD50 values of these compounds in NIH 3T3 fibroblasts shows that their susceptibility to these compounds in d ecreases the following order(:) CBD > 5-FU > DTM > CBG by MTT assay, CBD > 5-FU > CBG, DTM by SRB assay. These results suggest that DTM 2 has the most growth-inhibitory activity against KB cell lines.