TY  - CONF
AU  - Isca, Vera
AU  - Ntungwe, Epole
AU  - Bangay, Gabrielle
AU  - Princiotto, Salvatore
AU  - Dinić, Jelena
AU  - Pešić, Milica
AU  - Saraiva, Lucilia
AU  - Afonso, Carlos
AU  - Rijo, Patricia
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5611
AB  - Natural products are an important source of lead compounds for drug discovery. Plectranthus (Lamiaceae family) is an Old-World genus widely used in traditional medicine, whose species are rich in pharmacologically active compounds, specifically diterpenes. Two important lead molecules reported in Plectranthus spp. are the diterpenoids 7α-acetoxy-6β-hydroxyroyleanone (Roy, [Fig. 1]) and 6,7-dehydroroyleanone (DeRoy, [Fig. 1]) [1]. Previous studies reported in vitro activity of Roy and DeRoy against several breast cancer cell lines [1], [2]. Furthermore, in silico studies suggested promising interactions of these natural royleanones with protein kinase C (PKC) isoforms [2]. The key point of this work was to prepare new functionalized derivatives of Roy and DeRoy and evaluate their effect on two cancer targets, PKC isoforms and the efflux pump, P-glycoprotein (P-gp). New royleanone derivatives were obtained by hemi-synthesis, starting from Roy and DeRoy. Some of these compounds were evaluated as PKC (α, βI, δ, ε and ζ) activators. One benzoylated analogue showed the ability to selectively activate PKC-δ, while DeRoy displayed improved PKC activity, compared with the positive control, in all tested isoforms. Additionally, P-gp inhibitory potential was evaluated in human non-small cell lung carcinoma NCI-H460 and its MDR counterpart NCI-H460/R. Natural royleanones Roy and DeRoy showed similar cytotoxic activity against both NCI-H460 and MDR cancer cell lines. Interestingly, the benzoylated derivatives displayed the most promising results, showing an increased P-gp inhibitory activity and suggesting a relevant role of this moiety for the cytotoxic activity. Several other derivatives are currently under investigation as potential chemotherapeutic agents.
PB  - Thieme Medical Publishers
C3  - 70th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA); 2022 Aug 28-31; Thessaloniki, Greece
T1  - Natural and semi-synthetic royleanone diterpenoids from Plectranthus spp. as potential anti-tumoral agents
DO  - 10.1055/s-0042-1759260
SP  - 1540
ER  - 

@conference{
author = "Isca, Vera and Ntungwe, Epole and Bangay, Gabrielle and Princiotto, Salvatore and Dinić, Jelena and Pešić, Milica and Saraiva, Lucilia and Afonso, Carlos and Rijo, Patricia",
year = "2022",
abstract = "Natural products are an important source of lead compounds for drug discovery. Plectranthus (Lamiaceae family) is an Old-World genus widely used in traditional medicine, whose species are rich in pharmacologically active compounds, specifically diterpenes. Two important lead molecules reported in Plectranthus spp. are the diterpenoids 7α-acetoxy-6β-hydroxyroyleanone (Roy, [Fig. 1]) and 6,7-dehydroroyleanone (DeRoy, [Fig. 1]) [1]. Previous studies reported in vitro activity of Roy and DeRoy against several breast cancer cell lines [1], [2]. Furthermore, in silico studies suggested promising interactions of these natural royleanones with protein kinase C (PKC) isoforms [2]. The key point of this work was to prepare new functionalized derivatives of Roy and DeRoy and evaluate their effect on two cancer targets, PKC isoforms and the efflux pump, P-glycoprotein (P-gp). New royleanone derivatives were obtained by hemi-synthesis, starting from Roy and DeRoy. Some of these compounds were evaluated as PKC (α, βI, δ, ε and ζ) activators. One benzoylated analogue showed the ability to selectively activate PKC-δ, while DeRoy displayed improved PKC activity, compared with the positive control, in all tested isoforms. Additionally, P-gp inhibitory potential was evaluated in human non-small cell lung carcinoma NCI-H460 and its MDR counterpart NCI-H460/R. Natural royleanones Roy and DeRoy showed similar cytotoxic activity against both NCI-H460 and MDR cancer cell lines. Interestingly, the benzoylated derivatives displayed the most promising results, showing an increased P-gp inhibitory activity and suggesting a relevant role of this moiety for the cytotoxic activity. Several other derivatives are currently under investigation as potential chemotherapeutic agents.",
publisher = "Thieme Medical Publishers",
journal = "70th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA); 2022 Aug 28-31; Thessaloniki, Greece",
title = "Natural and semi-synthetic royleanone diterpenoids from Plectranthus spp. as potential anti-tumoral agents",
doi = "10.1055/s-0042-1759260",
pages = "1540"
}

Isca, V., Ntungwe, E., Bangay, G., Princiotto, S., Dinić, J., Pešić, M., Saraiva, L., Afonso, C.,& Rijo, P.. (2022). Natural and semi-synthetic royleanone diterpenoids from Plectranthus spp. as potential anti-tumoral agents. in 70th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA); 2022 Aug 28-31; Thessaloniki, Greece
Thieme Medical Publishers., 1540.
https://doi.org/10.1055/s-0042-1759260

Isca V, Ntungwe E, Bangay G, Princiotto S, Dinić J, Pešić M, Saraiva L, Afonso C, Rijo P. Natural and semi-synthetic royleanone diterpenoids from Plectranthus spp. as potential anti-tumoral agents. in 70th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA); 2022 Aug 28-31; Thessaloniki, Greece. 2022;:1540.
doi:10.1055/s-0042-1759260 .

Isca, Vera, Ntungwe, Epole, Bangay, Gabrielle, Princiotto, Salvatore, Dinić, Jelena, Pešić, Milica, Saraiva, Lucilia, Afonso, Carlos, Rijo, Patricia, "Natural and semi-synthetic royleanone diterpenoids from Plectranthus spp. as potential anti-tumoral agents" in 70th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA); 2022 Aug 28-31; Thessaloniki, Greece (2022):1540,
https://doi.org/10.1055/s-0042-1759260 . .