Afonso, Carlos

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  • Afonso, Carlos (4)
  • Afonso, Carlos AM (1)

Author's Bibliography

Cytotoxic Activity of diterpenes from Plectranthus spp. for MDR cancer therapy

Isca, Vera; Bangay, Gabrielle; Princiotto, Salvatore; Dinić, Jelena; Pešić, Milica; Saraíva, Lucília; Afonso, Carlos; Rijo, Patrícia

(STRATAGEM COST Action, 2022)

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 .

Natural and semi-synthetic royleanone diterpenoids from Plectranthus spp. as potential anti-tumoral agents

Isca, Vera; Ntungwe, Epole; Bangay, Gabrielle; Princiotto, Salvatore; Dinić, Jelena; Pešić, Milica; Saraiva, Lucilia; Afonso, Carlos; Rijo, Patricia

(Thieme Medical Publishers, 2022)

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 . .

Nanosystem of royleanone diterpenoids from Plectranthus spp to improve targeted delivery into cancer cells

Isca, Vera; Duro, Ana; Bangay, Gabrielle; Princiotto, Salvatore; Dinić, Jelena; Pešić, Milica; Saraiva, Lucilia; Afonso, Carlos; Rijo, Patricia

(ALIES - Associação Lusófona para o Desenvolvimento da Investigação e do Ensino das Ciências da Saúde, 2022)

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 . .

Royleanone Derivatives From Plectranthus spp. as a Novel Class of P-Glycoprotein Inhibitors

Garcia, Catarina; Isca, Vera; Pereira, Filipe; Monteiro, Carlos; Ntungwe, Epole; Sousa, Francisco; Dinić, Jelena; Holmstedt, Suvi; Roberto, Amílcar; Díaz-Lanza, Ana; Reis, Catarina; Pešić, Milica; Candeias, Nuno; Ferreira, Ricardo; Duarte, Noélia; Afonso, Carlos; Rijo, Patrícia

(Lausanne : Frontiers, 2020)

TY  - JOUR
AU  - Garcia, Catarina
AU  - Isca, Vera
AU  - Pereira, Filipe
AU  - Monteiro, Carlos
AU  - Ntungwe, Epole
AU  - Sousa, Francisco
AU  - Dinić, Jelena
AU  - Holmstedt, Suvi
AU  - Roberto, Amílcar
AU  - Díaz-Lanza, Ana
AU  - Reis, Catarina
AU  - Pešić, Milica
AU  - Candeias, Nuno
AU  - Ferreira, Ricardo
AU  - Duarte, Noélia
AU  - Afonso, Carlos
AU  - Rijo, Patrícia
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4261
AB  - Cancer is among the leading causes of death worldwide. One of the most challenging obstacles in cancer treatment is multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp) is associated with MDR. The growing incidence of cancer and the development of MDR drive the search for novel and more effective anticancer drugs to overcome the MDR problem. Royleanones are natural bioactive compounds frequently found in Plectranthus spp. The cytotoxic diterpene 6,7-dehydroroyleanone (1) is the main component of the P. madagascariensis (Pers.) Benth. essential oil, while 7α-acetoxy-6β-hydroxyroyleanone (2) can be isolated from acetonic extracts of P. grandidentatus Gürke. The reactivity of the natural royleanones 1 and 2 was explored to obtain a small library of new P-gp inhibitors. Four new derivatives (6,7-dehydro-12-O-tert-butyl-carbonate-royleanone (20), 6,7-dehydro-12-O-methylroyleanone (21), 6,7-dehydro-12-O-benzoylroyleanone (22), and 7α-acetoxy-6β-hydroxy-12-O-benzoylroyleanone (23) were obtained as pure with overall modest to excellent yields (21-97%). P-gp inhibition potential of the derivatives 20-23 was evaluated in human non-small cell lung carcinoma NCI-H460 and its MDR counterpart NCI-H460/R with the P-gp overexpression, through MTT assay. Previously prepared diterpene 7α-acetoxy-6β-benzoyloxy-12-O-(4-chloro)benzoylroyleanone (4), has also been tested. The P-gp inhibiting effects of compounds 1-4 were also assessed through a Rhodamine 123 accumulation assay. Derivatives 4 and 23 have significant P-gp inhibitory potential. Regarding stability and P-gp inhibition potential, results suggest that the formation of benzoyl esters is a more convenient approach for future derivatives with enhanced effect on the cell viability decrease. Compound 4 presented higher anti-P-gp potential than the natural diterpenes 1, 2, and 3, with comparable inhibitory potential to Dexverapamil. Moreover, derivative 4 showed the ability to sensitize the resistant NCI-H460/R cells to doxorubicin.
PB  - Lausanne : Frontiers
T2  - Frontiers in Pharmacology
T1  - Royleanone Derivatives From Plectranthus spp. as a Novel Class of P-Glycoprotein Inhibitors
VL  - 11
DO  - 10.3389/fphar.2020.557789
SP  - 557789
ER  - 
@article{
author = "Garcia, Catarina and Isca, Vera and Pereira, Filipe and Monteiro, Carlos and Ntungwe, Epole and Sousa, Francisco and Dinić, Jelena and Holmstedt, Suvi and Roberto, Amílcar and Díaz-Lanza, Ana and Reis, Catarina and Pešić, Milica and Candeias, Nuno and Ferreira, Ricardo and Duarte, Noélia and Afonso, Carlos and Rijo, Patrícia",
year = "2020",
abstract = "Cancer is among the leading causes of death worldwide. One of the most challenging obstacles in cancer treatment is multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp) is associated with MDR. The growing incidence of cancer and the development of MDR drive the search for novel and more effective anticancer drugs to overcome the MDR problem. Royleanones are natural bioactive compounds frequently found in Plectranthus spp. The cytotoxic diterpene 6,7-dehydroroyleanone (1) is the main component of the P. madagascariensis (Pers.) Benth. essential oil, while 7α-acetoxy-6β-hydroxyroyleanone (2) can be isolated from acetonic extracts of P. grandidentatus Gürke. The reactivity of the natural royleanones 1 and 2 was explored to obtain a small library of new P-gp inhibitors. Four new derivatives (6,7-dehydro-12-O-tert-butyl-carbonate-royleanone (20), 6,7-dehydro-12-O-methylroyleanone (21), 6,7-dehydro-12-O-benzoylroyleanone (22), and 7α-acetoxy-6β-hydroxy-12-O-benzoylroyleanone (23) were obtained as pure with overall modest to excellent yields (21-97%). P-gp inhibition potential of the derivatives 20-23 was evaluated in human non-small cell lung carcinoma NCI-H460 and its MDR counterpart NCI-H460/R with the P-gp overexpression, through MTT assay. Previously prepared diterpene 7α-acetoxy-6β-benzoyloxy-12-O-(4-chloro)benzoylroyleanone (4), has also been tested. The P-gp inhibiting effects of compounds 1-4 were also assessed through a Rhodamine 123 accumulation assay. Derivatives 4 and 23 have significant P-gp inhibitory potential. Regarding stability and P-gp inhibition potential, results suggest that the formation of benzoyl esters is a more convenient approach for future derivatives with enhanced effect on the cell viability decrease. Compound 4 presented higher anti-P-gp potential than the natural diterpenes 1, 2, and 3, with comparable inhibitory potential to Dexverapamil. Moreover, derivative 4 showed the ability to sensitize the resistant NCI-H460/R cells to doxorubicin.",
publisher = "Lausanne : Frontiers",
journal = "Frontiers in Pharmacology",
title = "Royleanone Derivatives From Plectranthus spp. as a Novel Class of P-Glycoprotein Inhibitors",
volume = "11",
doi = "10.3389/fphar.2020.557789",
pages = "557789"
}
Garcia, C., Isca, V., Pereira, F., Monteiro, C., Ntungwe, E., Sousa, F., Dinić, J., Holmstedt, S., Roberto, A., Díaz-Lanza, A., Reis, C., Pešić, M., Candeias, N., Ferreira, R., Duarte, N., Afonso, C.,& Rijo, P.. (2020). Royleanone Derivatives From Plectranthus spp. as a Novel Class of P-Glycoprotein Inhibitors. in Frontiers in Pharmacology
Lausanne : Frontiers., 11, 557789.
https://doi.org/10.3389/fphar.2020.557789
Garcia C, Isca V, Pereira F, Monteiro C, Ntungwe E, Sousa F, Dinić J, Holmstedt S, Roberto A, Díaz-Lanza A, Reis C, Pešić M, Candeias N, Ferreira R, Duarte N, Afonso C, Rijo P. Royleanone Derivatives From Plectranthus spp. as a Novel Class of P-Glycoprotein Inhibitors. in Frontiers in Pharmacology. 2020;11:557789.
doi:10.3389/fphar.2020.557789 .
Garcia, Catarina, Isca, Vera, Pereira, Filipe, Monteiro, Carlos, Ntungwe, Epole, Sousa, Francisco, Dinić, Jelena, Holmstedt, Suvi, Roberto, Amílcar, Díaz-Lanza, Ana, Reis, Catarina, Pešić, Milica, Candeias, Nuno, Ferreira, Ricardo, Duarte, Noélia, Afonso, Carlos, Rijo, Patrícia, "Royleanone Derivatives From Plectranthus spp. as a Novel Class of P-Glycoprotein Inhibitors" in Frontiers in Pharmacology, 11 (2020):557789,
https://doi.org/10.3389/fphar.2020.557789 . .
4
15
2
12

Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone obtained by optimized extraction.

Garcia, Catarina; Silva, Catarina Oliveira; Monteiro, Carlos M; Nicolai, Marisa; Viana, Ana; Andrade, Joana M; Barasoain, Isabel; Stanković, Tijana; Quintana, José; Hernández, Inmaculada; González, Ignacio; Estévez, Francisco; Díaz-Lanza, Ana M; Reis, Catarina P; Afonso, Carlos AM; Pešić, Milica; Rijo, Patrícia

(2018)

TY  - JOUR
AU  - Garcia, Catarina
AU  - Silva, Catarina Oliveira
AU  - Monteiro, Carlos M
AU  - Nicolai, Marisa
AU  - Viana, Ana
AU  - Andrade, Joana M
AU  - Barasoain, Isabel
AU  - Stanković, Tijana
AU  - Quintana, José
AU  - Hernández, Inmaculada
AU  - González, Ignacio
AU  - Estévez, Francisco
AU  - Díaz-Lanza, Ana M
AU  - Reis, Catarina P
AU  - Afonso, Carlos AM
AU  - Pešić, Milica
AU  - Rijo, Patrícia
PY  - 2018
UR  - https://www.future-science.com/doi/10.4155/fmc-2017-0239
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3086
AB  - AIM 6,7-dehydroroyleanone (DHR) is a cytotoxic abietane present in the essential oil of Plectranthus madagascariensis. METHODS/RESULTS Different extraction parameters were tested, and its extraction optimization was accomplished with a Clevenger apparatus-based hydrodistillation. After isolation, its effect on microtubules, P-glycoprotein and caspases was assessed on several cell lines and the compound was coupled with hybrid nanoparticles. The results show that DHR does not interfere with microtubule formation, but evades the resistance mechanisms of P-glycoprotein. Strong activation of caspases-3 and -9 indicates that DHR is able to induce apoptosis by triggering the intrinsic cell death pathway. Moreover, the assembly of DHR with hybrid nanoparticles was able to potentiate the effect of DHR in cancer cells. CONCLUSION DHR seems to be a promising starting material with anticancer properties to further be explored.
T2  - Future Medicinal Chemistry
T1  - Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone obtained by optimized extraction.
IS  - 10
VL  - 10
DO  - 10.4155/fmc-2017-0239
SP  - 1177
EP  - 1189
ER  - 
@article{
author = "Garcia, Catarina and Silva, Catarina Oliveira and Monteiro, Carlos M and Nicolai, Marisa and Viana, Ana and Andrade, Joana M and Barasoain, Isabel and Stanković, Tijana and Quintana, José and Hernández, Inmaculada and González, Ignacio and Estévez, Francisco and Díaz-Lanza, Ana M and Reis, Catarina P and Afonso, Carlos AM and Pešić, Milica and Rijo, Patrícia",
year = "2018",
abstract = "AIM 6,7-dehydroroyleanone (DHR) is a cytotoxic abietane present in the essential oil of Plectranthus madagascariensis. METHODS/RESULTS Different extraction parameters were tested, and its extraction optimization was accomplished with a Clevenger apparatus-based hydrodistillation. After isolation, its effect on microtubules, P-glycoprotein and caspases was assessed on several cell lines and the compound was coupled with hybrid nanoparticles. The results show that DHR does not interfere with microtubule formation, but evades the resistance mechanisms of P-glycoprotein. Strong activation of caspases-3 and -9 indicates that DHR is able to induce apoptosis by triggering the intrinsic cell death pathway. Moreover, the assembly of DHR with hybrid nanoparticles was able to potentiate the effect of DHR in cancer cells. CONCLUSION DHR seems to be a promising starting material with anticancer properties to further be explored.",
journal = "Future Medicinal Chemistry",
title = "Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone obtained by optimized extraction.",
number = "10",
volume = "10",
doi = "10.4155/fmc-2017-0239",
pages = "1177-1189"
}
Garcia, C., Silva, C. O., Monteiro, C. M., Nicolai, M., Viana, A., Andrade, J. M., Barasoain, I., Stanković, T., Quintana, J., Hernández, I., González, I., Estévez, F., Díaz-Lanza, A. M., Reis, C. P., Afonso, C. A., Pešić, M.,& Rijo, P.. (2018). Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone obtained by optimized extraction.. in Future Medicinal Chemistry, 10(10), 1177-1189.
https://doi.org/10.4155/fmc-2017-0239
Garcia C, Silva CO, Monteiro CM, Nicolai M, Viana A, Andrade JM, Barasoain I, Stanković T, Quintana J, Hernández I, González I, Estévez F, Díaz-Lanza AM, Reis CP, Afonso CA, Pešić M, Rijo P. Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone obtained by optimized extraction.. in Future Medicinal Chemistry. 2018;10(10):1177-1189.
doi:10.4155/fmc-2017-0239 .
Garcia, Catarina, Silva, Catarina Oliveira, Monteiro, Carlos M, Nicolai, Marisa, Viana, Ana, Andrade, Joana M, Barasoain, Isabel, Stanković, Tijana, Quintana, José, Hernández, Inmaculada, González, Ignacio, Estévez, Francisco, Díaz-Lanza, Ana M, Reis, Catarina P, Afonso, Carlos AM, Pešić, Milica, Rijo, Patrícia, "Anticancer properties of the abietane diterpene 6,7-dehydroroyleanone obtained by optimized extraction." in Future Medicinal Chemistry, 10, no. 10 (2018):1177-1189,
https://doi.org/10.4155/fmc-2017-0239 . .
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