Planta Med 2022; 88(15): 1419
DOI: 10.1055/s-0042-1758955
Egon-Stahl-Award in Bronze

“Isolation and design of diterpenoids from Plectranthus species”

Authors

  • E Ntungwe∗

    1   Research Center for Biosciences and Health Technologies, Lisboa, 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

  • A M Díaz-Lanza

    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

  • M Pešić

    3   Institute for Biological Research “Siniša Stanković” – National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Belgrade, Serbia

  • P Rijo

    1   Research Center for Biosciences and Health Technologies, Lisboa, Portugal
    4   Research Institute for Medicines (iMED.Ulisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649 – 003, Lisbon, Portugal
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P-gp is one of the major contributors to multidrug resistance (MDR) in cancer. Plectranthus plants are a potential source of diterpenoids reported as P-gp modulators [1]. The acetone extracts of sixteen Plectranthus spp. were prepared by ultrasound-assisted extraction method (10% (w/v). P. hadiensis and P. mutabilis extracts were found to be the most bioactive and the compounds responsible for their bioactivity were identified. 7α-acetoxy-6β-hydroxyroyleanon isolated from P. hadiensis was cytotoxic against the aggressive triple-negative breast cancer. This compound, its hemisynthetic derivative 7α-acetoxy-6β-benzoyloxyroyleanone (12BzRoy) and 6,7-dehydroroyleanone (DHR) from P. madagascariensis were employed as lead molecules for the synthesis of self-assembly nanoparticles using oleic acid (OA) and squalene (sq) as inducers. Roy-OA, DHR-sq, and 12BzRoy-sq drug conjugates were successfully synthesized. Roy-OA NPs released profile was determined. DHR.sq and, Roy-OA NPs were found to have less bioactivity when compared with DHR and Roy respectively. These findings suggest that nanoassemblies serve as prodrugs for the release of cytotoxic lead molecules.

Bio-guided fractionation of P. mutabilis extract resulted in the isolation of a new nor-abietane diterpene, (+)-(5S,10R)-10,11,12-trihydroxy-6,7-dioxo-20-nor-abieta-8,11,13-triene (1) alongside three known abietane-type diterpenoids, Coleon-U-quinone (2), 8α,9α-epoxycoleon-U-quinone (3), and Coleon U (4) ([Fig. 1]). Compounds 2, 3, and 4 inhibit P-gp activity in NCI-H460/R cells after 72 h of exposure and revert doxorubicin (DOX) resistance in subsequent combined treatment. All compounds did not influence the ABCB1 expression in NCI-H460/R cells, while the extract significantly increased it. Computational data indicates a biosynthetic relation between 2, 3, and 4 and suggest that both 2 and 3 are formed directly from 4 [2], [3].

Zoom
Fig. 1 Compound isolation from P. mutabilis: new nor-abietane diterpene, (+)-(5S,10R)-10,11,12-trihydroxy-6,7-dioxo-20-nor-abieta-8,11,13-triene (1), Coleon-U-quinone (2), 8α,9α-epoxycoleon-U-quinone (3), and Coleon U (4).


Publication History

Article published online:
12 December 2022

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Zoom
Fig. 1 Compound isolation from P. mutabilis: new nor-abietane diterpene, (+)-(5S,10R)-10,11,12-trihydroxy-6,7-dioxo-20-nor-abieta-8,11,13-triene (1), Coleon-U-quinone (2), 8α,9α-epoxycoleon-U-quinone (3), and Coleon U (4).