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

  • ACS Med Chem Lett. 2022 Mar 11;13(4):674-680. doi: 10.1021/acsmedchemlett.1c00711.
Epole N Ntungwe  1  2 ,  Sofija Jovanović Stojanov  3 ,  Noélia M Duarte  4 ,  Nuno R Candeias  5  6 ,  Ana M Díaz-Lanza  2 ,  Máté Vágvölgyi  7 ,  Attila Hunyadi  7 ,  Milica Pešić  3 ,  Patrícia Rijo  1  4
Affiliations
  • 1. CBIOS-Research Center for Biosciences & Health Technologies, Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisbon, Portugal.
  • 2. Pharmacology Area (Pharmacognosy Laboratory), New Antitumor Compounds: Toxic Action on Leukemia Cells Research Group, Faculty of Pharmacy, Department of Biomedical Sciences, University of Alcalá de Henares, Ctra. A2, Km 33.100-Campus Universitario, 28805 Alcalá de Henares, Spain.
  • 3. Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
  • 4. Research Institute for Medicines (iMED.Ulisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
  • 5. Faculty of Engineering and Natural Sciences, Tampere University, Korkeakoulunkatu 8, 33101 Tampere, Finland.
  • 6. LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
  • 7. Institute of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös str. 6, 6720 Szeged, Hungary.
PMID: 35450348 DOI: 10.1021/acsmedchemlett.1c00711
Abstract

In this study, a bioguided fractionation of Plectranthus mutabilis extract was performed by chromatographic methods. It yielded one new nor-abietane diterpene, mutabilol (1), and three known abietanes, coleon-U-quinone (2), 8α,9α-epoxycoleon-U-quinone (3), and coleon U (4). The abietane diterpenoid 5 was also tentatively identified using HPLC-MS/MS. Moreover, the extract profile and quantification of each isolated compound were determined by HPLC-DAD. Compound 4 was the major compound in the extract. Compounds 2-4 were found to be selective toward Cancer cell lines and were able to inhibit P-glycoprotein (P-gp) activity in NCI-H460/R cells at longer exposure of 72 h and consequently revert doxorubicin (DOX) resistance in subsequent combined treatment. None of the compounds influenced the P-gp expression in NCI-H460/R cells, while the extract significantly increased it.