TY  - CONF
AU  - Bangay, Gabrielle
AU  - Isca, Vera
AU  - Domínguez-Martín, Eva María
AU  - Santos, Daniel J.V.A.
AU  - Díaz-Lanza, Ana María
AU  - Saraiva, Lucília
AU  - Afonso, Carlos A.M.
AU  - Jovanović, Mirna
AU  - Pešić, Milica
AU  - Rijo, Patricia
PY  - 2023
UR  - https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0043-1774270
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6435
AB  - Multidrug resistant (MDR) cancer cases continue to increase, such that the search for novel and more effective anti-cancer therapeutics is of high priority. In some MDR cancers, the overexpression of membrane transport proteins, like P-glycoprotein (P-gp), continues to be a major impediment to successful therapy. Plectranthus genus (Lamiaceae), known for their medicinal and therapeutic properties, is a well-known source of bioactive diterpenoids, such as 7α-acetoxy-6β-hydroxyroyleanone (Roy) and 6,7- dehydroroyleanone (DeRoy). Based on in silico molecular docking studies, a small library of semi-synthetic derivates was prepared. The antitumoural activity of the compounds was assessed in resistant human cancer cell lines NCI-H460/R and DLD1-TxR. Cell viability was assessed using MTT assay and cell death induction by Annexin V/PI. Overall, it was demonstrated that three of the abietane diterpenoid analogues induced P-gp inhibition in MDR cancer cell lines, presenting novel selective compounds for the possible treatment of lung and colon cancer. Moreover, Roy and DeRoy nano-formulations were successfully prepared. DeRoy hybrid nanoparticles significantly increased the efficacy of DeRoy in NCI-H460 and NCI- H460/R. Roy, conjugated with oleic acid afforded self-assembly nanoparticles, to improve aqueous solubility and bioavailability of Roy. This new nano formulation did not decrease cell viability of Vero-E6 cells when compared to Roy with potential as a pro-drug delivery system. Currently, top hit derivatives are being prepared into nano-formulations for prospective pharmaceutical use as P-gp modulators.
PB  - Georg Thieme Verlag KG
C3  - 71st International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA); 2023 Jul 2-5; Dublin, Ireland
T1  - New formulations with royleanone derivatives from Plectranthus spp. to inhibit P-glycoprotein activity
DO  - 10.1055/s-0043-1774270
SP  - 1424
ER  - 

@conference{
author = "Bangay, Gabrielle and Isca, Vera and Domínguez-Martín, Eva María and Santos, Daniel J.V.A. and Díaz-Lanza, Ana María and Saraiva, Lucília and Afonso, Carlos A.M. and Jovanović, Mirna and Pešić, Milica and Rijo, Patricia",
year = "2023",
abstract = "Multidrug resistant (MDR) cancer cases continue to increase, such that the search for novel and more effective anti-cancer therapeutics is of high priority. In some MDR cancers, the overexpression of membrane transport proteins, like P-glycoprotein (P-gp), continues to be a major impediment to successful therapy. Plectranthus genus (Lamiaceae), known for their medicinal and therapeutic properties, is a well-known source of bioactive diterpenoids, such as 7α-acetoxy-6β-hydroxyroyleanone (Roy) and 6,7- dehydroroyleanone (DeRoy). Based on in silico molecular docking studies, a small library of semi-synthetic derivates was prepared. The antitumoural activity of the compounds was assessed in resistant human cancer cell lines NCI-H460/R and DLD1-TxR. Cell viability was assessed using MTT assay and cell death induction by Annexin V/PI. Overall, it was demonstrated that three of the abietane diterpenoid analogues induced P-gp inhibition in MDR cancer cell lines, presenting novel selective compounds for the possible treatment of lung and colon cancer. Moreover, Roy and DeRoy nano-formulations were successfully prepared. DeRoy hybrid nanoparticles significantly increased the efficacy of DeRoy in NCI-H460 and NCI- H460/R. Roy, conjugated with oleic acid afforded self-assembly nanoparticles, to improve aqueous solubility and bioavailability of Roy. This new nano formulation did not decrease cell viability of Vero-E6 cells when compared to Roy with potential as a pro-drug delivery system. Currently, top hit derivatives are being prepared into nano-formulations for prospective pharmaceutical use as P-gp modulators.",
publisher = "Georg Thieme Verlag KG",
journal = "71st International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA); 2023 Jul 2-5; Dublin, Ireland",
title = "New formulations with royleanone derivatives from Plectranthus spp. to inhibit P-glycoprotein activity",
doi = "10.1055/s-0043-1774270",
pages = "1424"
}

Bangay, G., Isca, V., Domínguez-Martín, E. M., Santos, D. J.V.A., Díaz-Lanza, A. M., Saraiva, L., Afonso, C. A.M., Jovanović, M., Pešić, M.,& Rijo, P.. (2023). New formulations with royleanone derivatives from Plectranthus spp. to inhibit P-glycoprotein activity. in 71st International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA); 2023 Jul 2-5; Dublin, Ireland
Georg Thieme Verlag KG., 1424.
https://doi.org/10.1055/s-0043-1774270

Bangay G, Isca V, Domínguez-Martín EM, Santos DJ, Díaz-Lanza AM, Saraiva L, Afonso CA, Jovanović M, Pešić M, Rijo P. New formulations with royleanone derivatives from Plectranthus spp. to inhibit P-glycoprotein activity. in 71st International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA); 2023 Jul 2-5; Dublin, Ireland. 2023;:1424.
doi:10.1055/s-0043-1774270 .

Bangay, Gabrielle, Isca, Vera, Domínguez-Martín, Eva María, Santos, Daniel J.V.A., Díaz-Lanza, Ana María, Saraiva, Lucília, Afonso, Carlos A.M., Jovanović, Mirna, Pešić, Milica, Rijo, Patricia, "New formulations with royleanone derivatives from Plectranthus spp. to inhibit P-glycoprotein activity" in 71st International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA); 2023 Jul 2-5; Dublin, Ireland (2023):1424,
https://doi.org/10.1055/s-0043-1774270 . .

TY  - CONF
AU  - Jovanović, Mirna
AU  - Bangay, Gabrielle
AU  - Jovanović Stojanov, Sofija
AU  - Dragoj, Miodrag
AU  - Stepanović, Ana
AU  - Lupšić, Ema
AU  - Podolski-Renić, Ana
AU  - Dinić, Jelena
AU  - Rijo, Patricia
AU  - Pešić, Milica
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5369
AB  - Plants of the genus Plectranthus (Lamiaceae) are used in traditional medicine. Here, the anti-cancer effects of the three abietane diterpenoid derivatives from Plectranthus species are described. Compounds’ effects (comp. 1 = VI31.1.1, comp. 2 = VI20.1.1, comp. 3 = RoyBz) were tested
in human lung cancer cells, in sensitive NCI-H460 and chemoresistant NCI-H460/R, as well as in colon cancer cells, sensitive DLD1, and hemoresistant DLD1-TxR. The resistant cells were more sensitive than corresponding parental cells to 1 and 2 in MTT assay, with IC50 values ranging from 3 to 10 μM. For the most potent 3 (IC50 as low as 1 μM), resistant cells had up to 2 times higher IC50 values than sensitive cells. The growth inhibition effect by all three compounds was more ronounced in cancer cells, compared to normal human fibroblasts (MRC-5). Only 2 induced a significant cell death effect showing 70% non-viable cells in NCI-H460. The effect the compoundsmight have on the P-gp extrusion pump was also tested using doxorubicin and rhodamine 123 accumulation assays. Compounds 1 and 2 caused a significant increase in the accumulation of both P-gp substrates, doxorubicin, and rhodamine 123. The compounds isolated from Plectranthus showed anticancer potential in lung and colon cancer cells. Importantly, they displayed colateral sensitivity - a phenomenon when the chemoresistant cells are more sensitive to the compounds than corresponding sensitive cells. The compounds inhibited the P-gp activity implying MDR modulating potential.
PB  - Belgrade: Serbian Plant Physiology Society
C3  - 4th International Conference on Plant Biology [and] 23rd SPPS Meeting; 2022 Oct 6-8; Belgrade, Serbia
T1  - Multidrug-resistant cancer cells are sensitive to abietane diterpenoids from Plectranthus species
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5369
ER  - 

@conference{
author = "Jovanović, Mirna and Bangay, Gabrielle and Jovanović Stojanov, Sofija and Dragoj, Miodrag and Stepanović, Ana and Lupšić, Ema and Podolski-Renić, Ana and Dinić, Jelena and Rijo, Patricia and Pešić, Milica",
year = "2022",
abstract = "Plants of the genus Plectranthus (Lamiaceae) are used in traditional medicine. Here, the anti-cancer effects of the three abietane diterpenoid derivatives from Plectranthus species are described. Compounds’ effects (comp. 1 = VI31.1.1, comp. 2 = VI20.1.1, comp. 3 = RoyBz) were tested
in human lung cancer cells, in sensitive NCI-H460 and chemoresistant NCI-H460/R, as well as in colon cancer cells, sensitive DLD1, and hemoresistant DLD1-TxR. The resistant cells were more sensitive than corresponding parental cells to 1 and 2 in MTT assay, with IC50 values ranging from 3 to 10 μM. For the most potent 3 (IC50 as low as 1 μM), resistant cells had up to 2 times higher IC50 values than sensitive cells. The growth inhibition effect by all three compounds was more ronounced in cancer cells, compared to normal human fibroblasts (MRC-5). Only 2 induced a significant cell death effect showing 70% non-viable cells in NCI-H460. The effect the compoundsmight have on the P-gp extrusion pump was also tested using doxorubicin and rhodamine 123 accumulation assays. Compounds 1 and 2 caused a significant increase in the accumulation of both P-gp substrates, doxorubicin, and rhodamine 123. The compounds isolated from Plectranthus showed anticancer potential in lung and colon cancer cells. Importantly, they displayed colateral sensitivity - a phenomenon when the chemoresistant cells are more sensitive to the compounds than corresponding sensitive cells. The compounds inhibited the P-gp activity implying MDR modulating potential.",
publisher = "Belgrade: Serbian Plant Physiology Society",
journal = "4th International Conference on Plant Biology [and] 23rd SPPS Meeting; 2022 Oct 6-8; Belgrade, Serbia",
title = "Multidrug-resistant cancer cells are sensitive to abietane diterpenoids from Plectranthus species",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5369"
}

Jovanović, M., Bangay, G., Jovanović Stojanov, S., Dragoj, M., Stepanović, A., Lupšić, E., Podolski-Renić, A., Dinić, J., Rijo, P.,& Pešić, M.. (2022). Multidrug-resistant cancer cells are sensitive to abietane diterpenoids from Plectranthus species. in 4th International Conference on Plant Biology [and] 23rd SPPS Meeting; 2022 Oct 6-8; Belgrade, Serbia
Belgrade: Serbian Plant Physiology Society..
https://hdl.handle.net/21.15107/rcub_ibiss_5369

Jovanović M, Bangay G, Jovanović Stojanov S, Dragoj M, Stepanović A, Lupšić E, Podolski-Renić A, Dinić J, Rijo P, Pešić M. Multidrug-resistant cancer cells are sensitive to abietane diterpenoids from Plectranthus species. in 4th International Conference on Plant Biology [and] 23rd SPPS Meeting; 2022 Oct 6-8; Belgrade, Serbia. 2022;.
https://hdl.handle.net/21.15107/rcub_ibiss_5369 .

Jovanović, Mirna, Bangay, Gabrielle, Jovanović Stojanov, Sofija, Dragoj, Miodrag, Stepanović, Ana, Lupšić, Ema, Podolski-Renić, Ana, Dinić, Jelena, Rijo, Patricia, Pešić, Milica, "Multidrug-resistant cancer cells are sensitive to abietane diterpenoids from Plectranthus species" in 4th International Conference on Plant Biology [and] 23rd SPPS Meeting; 2022 Oct 6-8; Belgrade, Serbia (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5369 .

TY  - CONF
AU  - Isca, Vera
AU  - Bangay, Gabrielle
AU  - Princiotto, Salvatore
AU  - Dinić, Jelena
AU  - Pešić, Milica
AU  - Saraíva, Lucília
AU  - Afonso, Carlos
AU  - Rijo, Patrícia
PY  - 2022
UR  - https://stratagem-cost.eu/wp-content/uploads/2022/07/Abstract-Book-Coimbra.pdf
UR  - https://stratagem-cost.eu/2022/04/stratagems-5th-co-located-annual-conference-and-wg3-4-training-school-to-be-held-in-coimbra-portugal-june-july-2022/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5622
AB  - Plectranthus genus (Lamiaceae family) is widely used in traditional medicine, and the presence of
pharmacologically active compounds, specifically diterpenes, is well reported. The cytotoxic diterpene
royleanones 7α-acetoxy-6β-hydroxyroyleanone (Roy) and 6,7-dehydroroyleanone (DeRoy) are the
major compounds of P. grandidentatus Gürke (acetonic extract) and P. madagascariensis (Pers.) Benth.
(essential oil), respectively. In this work, Roy and DeRoy were investigated as potential antitumor
agents through the activation of protein kinase C (PKC) isoforms (α, βI, δ, ε and ζ) and inhibition of
the efflux pump, P-glycoprotein (P-gp). Additionally, the reactivity of Roy and DeRoy was explored
to synthesize a library of new derivatives to be also evaluated as cytotoxic agents. PKC-α, βI, δ, ε, and
ζ activation was tested on a yeast-based screening assay. Interestingly, one benzoylated derivative
showed selective PKC-δ activation, while DeRoy exhibited enhanced PKC activity in all tested
isoforms, compared to the positive control. Moreover, inhibition of P-gp activity was evaluated in
human non-small cell lung carcinoma NCI-H460 and its MDR counterpart NCI-H460/R. It was
possible to identify an analogue with P-gp inhibitory activity higher than the natural diterpenes Roy
and DeRoy, and comparable to Dexverapamil (positive control). Several other semi-synthetic
products are currently under investigation as potential chemotherapeutic agents.
PB  - STRATAGEM COST Action
C3  - Abstract Book: STRATAGEM’s 5th Annual Meeting: New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumours; 2022 Jun 29 - Jul 1; Coimbra, Portugal
T1  - Cytotoxic Activity of diterpenes from Plectranthus spp. for MDR cancer therapy
SP  - 73
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5622
ER  - 

@conference{
author = "Isca, Vera and Bangay, Gabrielle and Princiotto, Salvatore and Dinić, Jelena and Pešić, Milica and Saraíva, Lucília and Afonso, Carlos and Rijo, Patrícia",
year = "2022",
abstract = "Plectranthus genus (Lamiaceae family) is widely used in traditional medicine, and the presence of
pharmacologically active compounds, specifically diterpenes, is well reported. The cytotoxic diterpene
royleanones 7α-acetoxy-6β-hydroxyroyleanone (Roy) and 6,7-dehydroroyleanone (DeRoy) are the
major compounds of P. grandidentatus Gürke (acetonic extract) and P. madagascariensis (Pers.) Benth.
(essential oil), respectively. In this work, Roy and DeRoy were investigated as potential antitumor
agents through the activation of protein kinase C (PKC) isoforms (α, βI, δ, ε and ζ) and inhibition of
the efflux pump, P-glycoprotein (P-gp). Additionally, the reactivity of Roy and DeRoy was explored
to synthesize a library of new derivatives to be also evaluated as cytotoxic agents. PKC-α, βI, δ, ε, and
ζ activation was tested on a yeast-based screening assay. Interestingly, one benzoylated derivative
showed selective PKC-δ activation, while DeRoy exhibited enhanced PKC activity in all tested
isoforms, compared to the positive control. Moreover, inhibition of P-gp activity was evaluated in
human non-small cell lung carcinoma NCI-H460 and its MDR counterpart NCI-H460/R. It was
possible to identify an analogue with P-gp inhibitory activity higher than the natural diterpenes Roy
and DeRoy, and comparable to Dexverapamil (positive control). Several other semi-synthetic
products are currently under investigation as potential chemotherapeutic agents.",
publisher = "STRATAGEM COST Action",
journal = "Abstract Book: STRATAGEM’s 5th Annual Meeting: New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumours; 2022 Jun 29 - Jul 1; Coimbra, Portugal",
title = "Cytotoxic Activity of diterpenes from Plectranthus spp. for MDR cancer therapy",
pages = "73",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5622"
}

Isca, V., Bangay, G., Princiotto, S., Dinić, J., Pešić, M., Saraíva, L., Afonso, C.,& Rijo, P.. (2022). Cytotoxic Activity of diterpenes from Plectranthus spp. for MDR cancer therapy. in Abstract Book: STRATAGEM’s 5th Annual Meeting: New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumours; 2022 Jun 29 - Jul 1; Coimbra, Portugal
STRATAGEM COST Action., 73.
https://hdl.handle.net/21.15107/rcub_ibiss_5622

Isca V, Bangay G, Princiotto S, Dinić J, Pešić M, Saraíva L, Afonso C, Rijo P. Cytotoxic Activity of diterpenes from Plectranthus spp. for MDR cancer therapy. in Abstract Book: STRATAGEM’s 5th Annual Meeting: New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumours; 2022 Jun 29 - Jul 1; Coimbra, Portugal. 2022;:73.
https://hdl.handle.net/21.15107/rcub_ibiss_5622 .

Isca, Vera, Bangay, Gabrielle, Princiotto, Salvatore, Dinić, Jelena, Pešić, Milica, Saraíva, Lucília, Afonso, Carlos, Rijo, Patrícia, "Cytotoxic Activity of diterpenes from Plectranthus spp. for MDR cancer therapy" in Abstract Book: STRATAGEM’s 5th Annual Meeting: New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumours; 2022 Jun 29 - Jul 1; Coimbra, Portugal (2022):73,
https://hdl.handle.net/21.15107/rcub_ibiss_5622 .

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 . .

TY  - CONF
AU  - Isca, Vera
AU  - Duro, Ana
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/123456789/5612
AB  - Nature is the most important source of novel pharmacologically active compounds for cancer
treatment. Plectranthus genus (Lamiaceae) has been widely used in traditional medicine and
seems to be promising for the research of new drug leads. In fact, Plectranthus spp. are rich in
cytotoxic diterpenoids, such as the 6,7-dehydroroyleanone (DeRoy) and the 7α-acetoxy-6β-
hydroxyroyleanone (Roy). (1) Royleanone diterpenoids are commonly very low water-soluble
compounds and nanotechnology can be employed to improve drug solubility and targeted
delivery: moreover, nanoformulations are often able to decrease the most frequent side effects
associated to chemotherapy. (2) Hybrid nanoparticles of DeRoy have shown an increased efficacy
of the natural royleanone on NCI-H460 and NCI-H460/R cell lines. (3) Additionally, self-
assembling nanoparticles combined with Roy reduced the cytotoxicity against normal cells (Vero-
E6) compared to parent compound (Roy) and displayed a low release of Roy at physiological pH.
(2) These results suggest that nano-assemblies of royleanones may act as a promising anticancer
strategy.
In this report, we describe the extraction and isolation of Roy from P. grandidentatus. Also, Roy
was derivatized with the goal of improving its antitumoral proprieties. Several derivatives were
prepared with overall good yields and are currently under in vitro antitumoral evaluation. So far,
two benzoylated derivatives revealed promising cytotoxic properties to be further exploited in
nanoformulations. Overall, we expect that derivatives in nanosystems can improve the drug
delivery and lead to an enhanced anticancer activity.
PB  - ALIES - Associação Lusófona para o Desenvolvimento da Investigação e do Ensino das Ciências da Saúde
C3  - Book of abstracts: InnovDelivery '22; I Lusophone Meeting on Innovative Delivery Systems; 2022 Jun 30; Virtual Meeting
T1  - Nanosystem of royleanone diterpenoids from Plectranthus spp to improve targeted delivery into cancer cells
DO  - 10.19277/bbr.19.2.289
SP  - 28
ER  - 

@conference{
author = "Isca, Vera and Duro, Ana and Bangay, Gabrielle and Princiotto, Salvatore and Dinić, Jelena and Pešić, Milica and Saraiva, Lucilia and Afonso, Carlos and Rijo, Patricia",
year = "2022",
abstract = "Nature is the most important source of novel pharmacologically active compounds for cancer
treatment. Plectranthus genus (Lamiaceae) has been widely used in traditional medicine and
seems to be promising for the research of new drug leads. In fact, Plectranthus spp. are rich in
cytotoxic diterpenoids, such as the 6,7-dehydroroyleanone (DeRoy) and the 7α-acetoxy-6β-
hydroxyroyleanone (Roy). (1) Royleanone diterpenoids are commonly very low water-soluble
compounds and nanotechnology can be employed to improve drug solubility and targeted
delivery: moreover, nanoformulations are often able to decrease the most frequent side effects
associated to chemotherapy. (2) Hybrid nanoparticles of DeRoy have shown an increased efficacy
of the natural royleanone on NCI-H460 and NCI-H460/R cell lines. (3) Additionally, self-
assembling nanoparticles combined with Roy reduced the cytotoxicity against normal cells (Vero-
E6) compared to parent compound (Roy) and displayed a low release of Roy at physiological pH.
(2) These results suggest that nano-assemblies of royleanones may act as a promising anticancer
strategy.
In this report, we describe the extraction and isolation of Roy from P. grandidentatus. Also, Roy
was derivatized with the goal of improving its antitumoral proprieties. Several derivatives were
prepared with overall good yields and are currently under in vitro antitumoral evaluation. So far,
two benzoylated derivatives revealed promising cytotoxic properties to be further exploited in
nanoformulations. Overall, we expect that derivatives in nanosystems can improve the drug
delivery and lead to an enhanced anticancer activity.",
publisher = "ALIES - Associação Lusófona para o Desenvolvimento da Investigação e do Ensino das Ciências da Saúde",
journal = "Book of abstracts: InnovDelivery '22; I Lusophone Meeting on Innovative Delivery Systems; 2022 Jun 30; Virtual Meeting",
title = "Nanosystem of royleanone diterpenoids from Plectranthus spp to improve targeted delivery into cancer cells",
doi = "10.19277/bbr.19.2.289",
pages = "28"
}

Isca, V., Duro, A., Bangay, G., Princiotto, S., Dinić, J., Pešić, M., Saraiva, L., Afonso, C.,& Rijo, P.. (2022). Nanosystem of royleanone diterpenoids from Plectranthus spp to improve targeted delivery into cancer cells. in Book of abstracts: InnovDelivery '22; I Lusophone Meeting on Innovative Delivery Systems; 2022 Jun 30; Virtual Meeting
ALIES - Associação Lusófona para o Desenvolvimento da Investigação e do Ensino das Ciências da Saúde., 28.
https://doi.org/10.19277/bbr.19.2.289

Isca V, Duro A, Bangay G, Princiotto S, Dinić J, Pešić M, Saraiva L, Afonso C, Rijo P. Nanosystem of royleanone diterpenoids from Plectranthus spp to improve targeted delivery into cancer cells. in Book of abstracts: InnovDelivery '22; I Lusophone Meeting on Innovative Delivery Systems; 2022 Jun 30; Virtual Meeting. 2022;:28.
doi:10.19277/bbr.19.2.289 .

Isca, Vera, Duro, Ana, Bangay, Gabrielle, Princiotto, Salvatore, Dinić, Jelena, Pešić, Milica, Saraiva, Lucilia, Afonso, Carlos, Rijo, Patricia, "Nanosystem of royleanone diterpenoids from Plectranthus spp to improve targeted delivery into cancer cells" in Book of abstracts: InnovDelivery '22; I Lusophone Meeting on Innovative Delivery Systems; 2022 Jun 30; Virtual Meeting (2022):28,
https://doi.org/10.19277/bbr.19.2.289 . .

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 . .