C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators

In this study, a bioguided fractionation ofPlectranthus mutabilisextract was performed by chromatographicmethods. It yielded one newnor-abietane diterpene, mutabilol (1),and three known abietanes, coleon-U-quinone (2), 8 alpha,9 alpha-epoxycoleon-U-quinone (3), and coleon U (4). The abietanediterpenoid5was also tentatively identified using HPLC-MS/MS.Moreover, the extract profile and quantification of each isolatedcompound were determined by HPLC-DAD. Compound4was themajor compound in the extract. Compounds2-4were found to beselective toward cancer cell lines and were able to inhibit P-glycoprotein (P-gp) activity in NCI-H460/R cells at longerexposure of 72 h and consequently revert doxorubicin (DOX)resistance in subsequent combined treatment. None of thecompounds influenced the P-gp expression in NCI-H460/R cells, while the extract significantly increased it