TY  - JOUR
AU  - Ntungwe, Epole N.
AU  - Jovanović Stojanov, Sofija
AU  - Duarte, Noélia M.
AU  - Candeias, Nuno R.
AU  - Díaz-Lanza, Ana M.
AU  - Vágvölgyi, Máté
AU  - Hunyadi, Attila
AU  - Pešić, Milica
AU  - Rijo, Patrícia
PY  - 2022
UR  - https://pubs.acs.org/doi/10.1021/acsmedchemlett.1c00711
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9014510
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4945
AB  - In this study, a bioguided fractionation of Plectranthus mutabilis extract was performed by chromatographic methods. It yielded one new nor-abietane diterpene, mutabilol (1), and three known abietanes, coleon-U-quinone (2), 8α,9α-epoxycoleon-U-quinone (3), and coleon U (4). The abietane diterpenoid 5 was also tentatively identified using HPLC-MS/MS. Moreover, the extract profile and quantification of each isolated compound were determined by HPLC-DAD. Compound 4 was the major compound in the extract. Compounds 2-4 were found to be selective toward cancer cell lines and were able to inhibit P-glycoprotein (P-gp) activity in NCI-H460/R cells at longer exposure of 72 h and consequently revert doxorubicin (DOX) resistance in subsequent combined treatment. None of the compounds influenced the P-gp expression in NCI-H460/R cells, while the extract significantly increased it.
T2  - ACS Medicinal Chemistry Letters
T1  - C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators.
IS  - 4
VL  - 13
DO  - 10.1021/acsmedchemlett.1c00711
SP  - 674
EP  - 680
ER  - 

@article{
author = "Ntungwe, Epole N. and Jovanović Stojanov, Sofija and Duarte, Noélia M. and Candeias, Nuno R. and Díaz-Lanza, Ana M. and Vágvölgyi, Máté and Hunyadi, Attila and Pešić, Milica and Rijo, Patrícia",
year = "2022",
abstract = "In this study, a bioguided fractionation of Plectranthus mutabilis extract was performed by chromatographic methods. It yielded one new nor-abietane diterpene, mutabilol (1), and three known abietanes, coleon-U-quinone (2), 8α,9α-epoxycoleon-U-quinone (3), and coleon U (4). The abietane diterpenoid 5 was also tentatively identified using HPLC-MS/MS. Moreover, the extract profile and quantification of each isolated compound were determined by HPLC-DAD. Compound 4 was the major compound in the extract. Compounds 2-4 were found to be selective toward cancer cell lines and were able to inhibit P-glycoprotein (P-gp) activity in NCI-H460/R cells at longer exposure of 72 h and consequently revert doxorubicin (DOX) resistance in subsequent combined treatment. None of the compounds influenced the P-gp expression in NCI-H460/R cells, while the extract significantly increased it.",
journal = "ACS Medicinal Chemistry Letters",
title = "C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators.",
number = "4",
volume = "13",
doi = "10.1021/acsmedchemlett.1c00711",
pages = "674-680"
}

Ntungwe, E. N., Jovanović Stojanov, S., Duarte, N. M., Candeias, N. R., Díaz-Lanza, A. M., Vágvölgyi, M., Hunyadi, A., Pešić, M.,& Rijo, P.. (2022). C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators.. in ACS Medicinal Chemistry Letters, 13(4), 674-680.
https://doi.org/10.1021/acsmedchemlett.1c00711

Ntungwe EN, Jovanović Stojanov S, Duarte NM, Candeias NR, Díaz-Lanza AM, Vágvölgyi M, Hunyadi A, Pešić M, Rijo P. C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators.. in ACS Medicinal Chemistry Letters. 2022;13(4):674-680.
doi:10.1021/acsmedchemlett.1c00711 .

Ntungwe, Epole N., Jovanović Stojanov, Sofija, Duarte, Noélia M., Candeias, Nuno R., Díaz-Lanza, Ana M., Vágvölgyi, Máté, Hunyadi, Attila, Pešić, Milica, Rijo, Patrícia, "C20-nor-Abietane and Three Abietane Diterpenoids from Plectranthus mutabilis Leaves as P-Glycoprotein Modulators." in ACS Medicinal Chemistry Letters, 13, no. 4 (2022):674-680,
https://doi.org/10.1021/acsmedchemlett.1c00711 . .

TY  - JOUR
AU  - Latif, Ahmed Dhahir
AU  - Jernei, Tamás
AU  - Podolski-Renić, Ana
AU  - Kuo, Ching-Ying
AU  - Vágvölgyi, Máté
AU  - Girst, Gábor
AU  - Zupkó, István
AU  - Develi, Sedef
AU  - Ulukaya, Engin
AU  - Wang, Hui-Chun
AU  - Pešić, Milica
AU  - Csámpai, Antal
AU  - Hunyadi, Attila
PY  - 2020
UR  - https://www.mdpi.com/2076-3921/9/6/519
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3720
AB  - Hybrid compounds combine fragments with complementary targets to achieve a common pharmacological goal. This approach represents an increasingly popular strategy for drug discovery. In this work, we aimed to design antitumor hybrid compounds based on an inhibitor of ataxia-telangiectasia and Rad3-related protein (ATR)-dependent signaling, protoapigenone, and a pro-oxidant ferrocene or chalcone fragment. Four new triazole-coupled hybrids were prepared. The compounds were cytotoxic against human breast cancer cell lines in vitro, showing IC50 values in the sub-micromolar range. The nature of interactions between relevant fragments of the hybrids was evaluated by the Chou–Talalay method. Experimental combination treatment with the fragments showed additive effects or slight/moderate synergism, while strong synergism was observed when the fragments were virtually combined into their hybrids, suggesting a relevant pharmacological benefit of the coupling. All hybrids were strong inhibitors of the ATR-mediated activation of Chk1, and they interfered with the redox balance of the cells leading to mitochondrial membrane depolarization. Additionally, they induced late apoptosis and primary necrosis in MDA-MB-231 and MCF-7 breast cancer cells, respectively. Our results demonstrate that coupling the ATR-dependent signaling inhibitor protoflavone with a pro-oxidant chalcone dramatically increases the antitumor activity compared with either fragment alone. Such compounds may offer an attractive novel strategy for the treatment of various cancers.
PB  - MDPI AG
T2  - Antioxidants
T1  - Protoflavone-Chalcone Hybrids Exhibit Enhanced Antitumor Action through Modulating Redox Balance, Depolarizing the Mitochondrial Membrane, and Inhibiting ATR-Dependent Signaling
IS  - 6
VL  - 9
DO  - 10.3390/antiox9060519
SP  - 519
ER  - 

@article{
author = "Latif, Ahmed Dhahir and Jernei, Tamás and Podolski-Renić, Ana and Kuo, Ching-Ying and Vágvölgyi, Máté and Girst, Gábor and Zupkó, István and Develi, Sedef and Ulukaya, Engin and Wang, Hui-Chun and Pešić, Milica and Csámpai, Antal and Hunyadi, Attila",
year = "2020",
abstract = "Hybrid compounds combine fragments with complementary targets to achieve a common pharmacological goal. This approach represents an increasingly popular strategy for drug discovery. In this work, we aimed to design antitumor hybrid compounds based on an inhibitor of ataxia-telangiectasia and Rad3-related protein (ATR)-dependent signaling, protoapigenone, and a pro-oxidant ferrocene or chalcone fragment. Four new triazole-coupled hybrids were prepared. The compounds were cytotoxic against human breast cancer cell lines in vitro, showing IC50 values in the sub-micromolar range. The nature of interactions between relevant fragments of the hybrids was evaluated by the Chou–Talalay method. Experimental combination treatment with the fragments showed additive effects or slight/moderate synergism, while strong synergism was observed when the fragments were virtually combined into their hybrids, suggesting a relevant pharmacological benefit of the coupling. All hybrids were strong inhibitors of the ATR-mediated activation of Chk1, and they interfered with the redox balance of the cells leading to mitochondrial membrane depolarization. Additionally, they induced late apoptosis and primary necrosis in MDA-MB-231 and MCF-7 breast cancer cells, respectively. Our results demonstrate that coupling the ATR-dependent signaling inhibitor protoflavone with a pro-oxidant chalcone dramatically increases the antitumor activity compared with either fragment alone. Such compounds may offer an attractive novel strategy for the treatment of various cancers.",
publisher = "MDPI AG",
journal = "Antioxidants",
title = "Protoflavone-Chalcone Hybrids Exhibit Enhanced Antitumor Action through Modulating Redox Balance, Depolarizing the Mitochondrial Membrane, and Inhibiting ATR-Dependent Signaling",
number = "6",
volume = "9",
doi = "10.3390/antiox9060519",
pages = "519"
}

Latif, A. D., Jernei, T., Podolski-Renić, A., Kuo, C., Vágvölgyi, M., Girst, G., Zupkó, I., Develi, S., Ulukaya, E., Wang, H., Pešić, M., Csámpai, A.,& Hunyadi, A.. (2020). Protoflavone-Chalcone Hybrids Exhibit Enhanced Antitumor Action through Modulating Redox Balance, Depolarizing the Mitochondrial Membrane, and Inhibiting ATR-Dependent Signaling. in Antioxidants
MDPI AG., 9(6), 519.
https://doi.org/10.3390/antiox9060519

Latif AD, Jernei T, Podolski-Renić A, Kuo C, Vágvölgyi M, Girst G, Zupkó I, Develi S, Ulukaya E, Wang H, Pešić M, Csámpai A, Hunyadi A. Protoflavone-Chalcone Hybrids Exhibit Enhanced Antitumor Action through Modulating Redox Balance, Depolarizing the Mitochondrial Membrane, and Inhibiting ATR-Dependent Signaling. in Antioxidants. 2020;9(6):519.
doi:10.3390/antiox9060519 .

Latif, Ahmed Dhahir, Jernei, Tamás, Podolski-Renić, Ana, Kuo, Ching-Ying, Vágvölgyi, Máté, Girst, Gábor, Zupkó, István, Develi, Sedef, Ulukaya, Engin, Wang, Hui-Chun, Pešić, Milica, Csámpai, Antal, Hunyadi, Attila, "Protoflavone-Chalcone Hybrids Exhibit Enhanced Antitumor Action through Modulating Redox Balance, Depolarizing the Mitochondrial Membrane, and Inhibiting ATR-Dependent Signaling" in Antioxidants, 9, no. 6 (2020):519,
https://doi.org/10.3390/antiox9060519 . .