TY  - CONF
AU  - Bangay, Gabrielle
AU  - Isca, Vera M. S.
AU  - Dos Santos, Daniel J. V. A.
AU  - Ferreira, Ricardo J.
AU  - Princiotto, Salvatore
AU  - Jovanović, Mirna
AU  - Pešić, Milica
AU  - Rijo, Patricia
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5471
AB  - The number of multidrug resistant (MDR) cancer cases across the globe is continuing to rise,
such that the search for novel anti-cancer therapeutics is paramount. For instance, the overexpression
of membrane transport proteins, such as P-glycoprotein (P-gp), or the selective modulation of protein
kinases C (PKC) isoforms continues to be a major impediment to effective therapy. Known for
their medicinal properties, species from Plectranthus have been reported to have cytotoxicity against
various cancer cell lines due to diterpenes, such as 7 -acetoxy-6 -hydroxyroyleanone (Roy) and 6,7-
dehydroroyleanone (DeRoy). Based on molecular docking simulations, 10 semi-synthetic derivatives
of Roy that displayed strong P-gp interactions in silico were prepared. The antitumoral activity was
evaluated in resistant human cancer cell lines NCI-H460/R and DLD1-TxR, showing three derivatives
having the most prominent selectivity towards cancer cells, compared to normal lung fibroblasts
MRC5. Moreover, they showed a reduction in P-gp activity in Rho123 accumulation and indicated
P-gp inhibition in the DOX accumulation assay using the same resistant cell lines. Overall, it was
demonstrated that three abietane diterpenoids induced P-gp inhibition in MDR cancer cell lines. As
regards the PKC activity, further analogues were tested as PKC ( ,  I,  , " and  ) modulators; one
benzoylated derivative showed the ability to selectively activate PKC- , while the natural compound
DeRoy displayed improved PKC activity, compared with the positive control, in all tested isoforms.
Further investigations are ongoing to prepare analogues of other biologically active diterpenoids to
obtain potential hits as P-gp and PKC modulators.
PB  - Basel: MDPI
C3  - The 8th International Electronic Conference on Medicinal Chemistry; 2022 Nov 1-30; Virtual Event
T1  - Royleanone Analogues from Plectranthus spp. Demonstrate P-gp Inhibition and PKC Modulation
DO  - 10.3390/ECMC2022-13459
SP  - 144
ER  - 

@conference{
author = "Bangay, Gabrielle and Isca, Vera M. S. and Dos Santos, Daniel J. V. A. and Ferreira, Ricardo J. and Princiotto, Salvatore and Jovanović, Mirna and Pešić, Milica and Rijo, Patricia",
year = "2022",
abstract = "The number of multidrug resistant (MDR) cancer cases across the globe is continuing to rise,
such that the search for novel anti-cancer therapeutics is paramount. For instance, the overexpression
of membrane transport proteins, such as P-glycoprotein (P-gp), or the selective modulation of protein
kinases C (PKC) isoforms continues to be a major impediment to effective therapy. Known for
their medicinal properties, species from Plectranthus have been reported to have cytotoxicity against
various cancer cell lines due to diterpenes, such as 7 -acetoxy-6 -hydroxyroyleanone (Roy) and 6,7-
dehydroroyleanone (DeRoy). Based on molecular docking simulations, 10 semi-synthetic derivatives
of Roy that displayed strong P-gp interactions in silico were prepared. The antitumoral activity was
evaluated in resistant human cancer cell lines NCI-H460/R and DLD1-TxR, showing three derivatives
having the most prominent selectivity towards cancer cells, compared to normal lung fibroblasts
MRC5. Moreover, they showed a reduction in P-gp activity in Rho123 accumulation and indicated
P-gp inhibition in the DOX accumulation assay using the same resistant cell lines. Overall, it was
demonstrated that three abietane diterpenoids induced P-gp inhibition in MDR cancer cell lines. As
regards the PKC activity, further analogues were tested as PKC ( ,  I,  , " and  ) modulators; one
benzoylated derivative showed the ability to selectively activate PKC- , while the natural compound
DeRoy displayed improved PKC activity, compared with the positive control, in all tested isoforms.
Further investigations are ongoing to prepare analogues of other biologically active diterpenoids to
obtain potential hits as P-gp and PKC modulators.",
publisher = "Basel: MDPI",
journal = "The 8th International Electronic Conference on Medicinal Chemistry; 2022 Nov 1-30; Virtual Event",
title = "Royleanone Analogues from Plectranthus spp. Demonstrate P-gp Inhibition and PKC Modulation",
doi = "10.3390/ECMC2022-13459",
pages = "144"
}

Bangay, G., Isca, V. M. S., Dos Santos, D. J. V. A., Ferreira, R. J., Princiotto, S., Jovanović, M., Pešić, M.,& Rijo, P.. (2022). Royleanone Analogues from Plectranthus spp. Demonstrate P-gp Inhibition and PKC Modulation. in The 8th International Electronic Conference on Medicinal Chemistry; 2022 Nov 1-30; Virtual Event
Basel: MDPI., 144.
https://doi.org/10.3390/ECMC2022-13459

Bangay G, Isca VMS, Dos Santos DJVA, Ferreira RJ, Princiotto S, Jovanović M, Pešić M, Rijo P. Royleanone Analogues from Plectranthus spp. Demonstrate P-gp Inhibition and PKC Modulation. in The 8th International Electronic Conference on Medicinal Chemistry; 2022 Nov 1-30; Virtual Event. 2022;:144.
doi:10.3390/ECMC2022-13459 .

Bangay, Gabrielle, Isca, Vera M. S., Dos Santos, Daniel J. V. A., Ferreira, Ricardo J., Princiotto, Salvatore, Jovanović, Mirna, Pešić, Milica, Rijo, Patricia, "Royleanone Analogues from Plectranthus spp. Demonstrate P-gp Inhibition and PKC Modulation" in The 8th International Electronic Conference on Medicinal Chemistry; 2022 Nov 1-30; Virtual Event (2022):144,
https://doi.org/10.3390/ECMC2022-13459 . .