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  - Ntungwe, Epole
AU  - Jovanović Stojanov, Sofija
AU  - Duarte, Noélia
AU  - R. Candeias, Nuno
AU  - Díaz-Lanza, Ana María
AU  - Pešić, Milica
AU  - Rijo, Patrícia
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5610
UR  - https://sciforum.net/paper/view/13460
AB  - The development of multidrug resistance (MDR) is one of the major challenges in the successful treatment of cancer. MDR is often associated with the P-glycoprotein efflux pump. Natural products are a source of promising lead compounds to overcome MDR and, among them, diterpenoids from Plectranthus spp. are known as P-gp modulators. Bioguided fractionation of P. mutabilis acetone extract led to the isolation of one new nor-abietane diterpene, mutabilol (1), and three coleon compounds (coleon-U-quinone (2), 8α,9α-epoxycoleon-U-quinone (3), and coleon U (4)). Moreover, an additional acetoxy derivative of an abietane diterpenoid was tentatively identified using HPLC-MS/MS. The compounds were quantified using HPLC-DAD and coleon U was found to be the major compound in the extract. Using computational studies, a biosynthetic relationship between compounds 2 - 4 revealed that both compounds 2 and 3 were formed directly from compound 4. Compounds 2 - 4 were found to be selective towards the cancer cell lines and their anticancer effect was not compromised by the P-gp activity in resistant NCI-H460/R cells. Importantly 2, 3, and 4 were able to inhibit P-gp activity in NCI-H460/R cells at longer exposure (72 h) and revert doxorubicin (DOX) resistance in combined treatment. None of the compounds influenced the P-gp expression in NCI-H460/R cells, while the extract significantly increased it. Our study identified abietane diterpenoids from P. mutabilis that can evade MDR in cancer cells and inhibit the P-gp activity in prolonged treatment.
PB  - SCIForum
C3  - The 8th International Electronic Conference on Medicinal Chemistry; 2022 Nov 1-30; Virtual Event
T1  - P-gp modulation and biosynthetic relationship of isolated compounds from Plectranthus mutabilis Codd.
DO  - 10.3390/ECMC2022-13460
ER  - 

@conference{
author = "Ntungwe, Epole and Jovanović Stojanov, Sofija and Duarte, Noélia and R. Candeias, Nuno and Díaz-Lanza, Ana María and Pešić, Milica and Rijo, Patrícia",
year = "2022",
abstract = "The development of multidrug resistance (MDR) is one of the major challenges in the successful treatment of cancer. MDR is often associated with the P-glycoprotein efflux pump. Natural products are a source of promising lead compounds to overcome MDR and, among them, diterpenoids from Plectranthus spp. are known as P-gp modulators. Bioguided fractionation of P. mutabilis acetone extract led to the isolation of one new nor-abietane diterpene, mutabilol (1), and three coleon compounds (coleon-U-quinone (2), 8α,9α-epoxycoleon-U-quinone (3), and coleon U (4)). Moreover, an additional acetoxy derivative of an abietane diterpenoid was tentatively identified using HPLC-MS/MS. The compounds were quantified using HPLC-DAD and coleon U was found to be the major compound in the extract. Using computational studies, a biosynthetic relationship between compounds 2 - 4 revealed that both compounds 2 and 3 were formed directly from compound 4. Compounds 2 - 4 were found to be selective towards the cancer cell lines and their anticancer effect was not compromised by the P-gp activity in resistant NCI-H460/R cells. Importantly 2, 3, and 4 were able to inhibit P-gp activity in NCI-H460/R cells at longer exposure (72 h) and revert doxorubicin (DOX) resistance in combined treatment. None of the compounds influenced the P-gp expression in NCI-H460/R cells, while the extract significantly increased it. Our study identified abietane diterpenoids from P. mutabilis that can evade MDR in cancer cells and inhibit the P-gp activity in prolonged treatment.",
publisher = "SCIForum",
journal = "The 8th International Electronic Conference on Medicinal Chemistry; 2022 Nov 1-30; Virtual Event",
title = "P-gp modulation and biosynthetic relationship of isolated compounds from Plectranthus mutabilis Codd.",
doi = "10.3390/ECMC2022-13460"
}

Ntungwe, E., Jovanović Stojanov, S., Duarte, N., R. Candeias, N., Díaz-Lanza, A. M., Pešić, M.,& Rijo, P.. (2022). P-gp modulation and biosynthetic relationship of isolated compounds from Plectranthus mutabilis Codd.. in The 8th International Electronic Conference on Medicinal Chemistry; 2022 Nov 1-30; Virtual Event
SCIForum..
https://doi.org/10.3390/ECMC2022-13460

Ntungwe E, Jovanović Stojanov S, Duarte N, R. Candeias N, Díaz-Lanza AM, Pešić M, Rijo P. P-gp modulation and biosynthetic relationship of isolated compounds from Plectranthus mutabilis Codd.. in The 8th International Electronic Conference on Medicinal Chemistry; 2022 Nov 1-30; Virtual Event. 2022;.
doi:10.3390/ECMC2022-13460 .

Ntungwe, Epole, Jovanović Stojanov, Sofija, Duarte, Noélia, R. Candeias, Nuno, Díaz-Lanza, Ana María, Pešić, Milica, Rijo, Patrícia, "P-gp modulation and biosynthetic relationship of isolated compounds from Plectranthus mutabilis Codd." in The 8th International Electronic Conference on Medicinal Chemistry; 2022 Nov 1-30; Virtual Event (2022),
https://doi.org/10.3390/ECMC2022-13460 . .