TY  - JOUR
AU  - Isca, Vera M. S.
AU  - Senćanski, Milan V.
AU  - Filipović, Nenad R.
AU  - Dos Santos, Daniel J. V. A.
AU  - Čipak Gašparović, Ana
AU  - Saraiva, Lucilia
AU  - Afonso, Carlos A M
AU  - Rijo, Patrícia
AU  - Garcia-Sosa, Alfonso T
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9017
AB  - Plants have been used for centuries to treat several illnesses. The Plectranthus genus has a vast variety of species that has allowed the isolation of cytotoxic compounds with notable activities. The abietane diterpenes 6,7-dehydroroyleanone (DeRoy, 1), 7α-acetoxy-6β-hydroxyroyleanone (Roy, 2), and Parvifloron D (ParvD, 3) were obtained from Plectranthus spp. and showed promising biological activities, such as cytotoxicity. The inhibitory effects of the different natural abietanes (1-3) were compared in MFC7, SkBr3, and SUM159 cell lines, as well as SUM159 grown in cancer stem cell-inducing conditions. Based on the royleanones’ bioactivity, the derivatives RoyBz (4), RoyBzCl (5), RoyPr2 (6), and DihydroxyRoy (7), previously obtained from 2, were selected for further studies. Protein kinases C (PKCs) are involved in several carcinogenic processes. Thus, PKCs are potential targets for cancer therapy. To date, the portfolio of available PKC modulators remains very limited due to the difficulty of designing isozyme-selective PKC modulators. As such, molecular docking was used to evaluate royleanones 1-6 as predicted isozyme-selective PKC binders. Subtle changes in the binding site of each PKC isoform change the predicted interaction profiles of the ligands. Subtle changes in royleanone substitution patterns, such as a double substitution only with non-substituted phenyls, or hydroxybenzoate at position four that flips the binding mode of ParvD (3), can increase the predicted interactions in certain PKC subtypes.
AB  - Plants have been used for centuries to treat several illnesses. The Plectranthus genus has a vast variety of species that has allowed the isolation of cytotoxic compounds with notable activities. The abietane diterpenes 6,7-dehydroroyleanone (DeRoy, 1), 7α-acetoxy-6β-hydroxyroyleanone (Roy, 2), and Parvifloron D (ParvD, 3) were obtained from Plectranthus spp. and showed promising biological activities, such as cytotoxicity. The inhibitory effects of the different natural abietanes (1-3) were compared in MFC7, SkBr3, and SUM159 cell lines, as well as SUM159 grown in cancer stem cell-inducing conditions. Based on the royleanones’ bioactivity, the derivatives RoyBz (4), RoyBzCl (5), RoyPr2 (6), and DihydroxyRoy (7), previously obtained from 2, were selected for further studies. Protein kinases C (PKCs) are involved in several carcinogenic processes. Thus, PKCs are potential targets for cancer therapy. To date, the portfolio of available PKC modulators remains very limited due to the difficulty of designing isozyme-selective PKC modulators. As such, molecular docking was used to evaluate royleanones 1-6 as predicted isozyme-selective PKC binders. Subtle changes in the binding site of each PKC isoform change the predicted interaction profiles of the ligands. Subtle changes in royleanone substitution patterns, such as a double substitution only with non-substituted phenyls, or hydroxybenzoate at position four that flips the binding mode of ParvD (3), can increase the predicted interactions in certain PKC subtypes.
T2  - International Journal of Molecular Sciences
T1  - Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones
VL  - 21
IS  - 10
SP  - 3671
DO  - 10.3390/ijms21103671
ER  - 

@article{
author = "Isca, Vera M. S. and Senćanski, Milan V. and Filipović, Nenad R. and Dos Santos, Daniel J. V. A. and Čipak Gašparović, Ana and Saraiva, Lucilia and Afonso, Carlos A M and Rijo, Patrícia and Garcia-Sosa, Alfonso T",
year = "2020",
abstract = "Plants have been used for centuries to treat several illnesses. The Plectranthus genus has a vast variety of species that has allowed the isolation of cytotoxic compounds with notable activities. The abietane diterpenes 6,7-dehydroroyleanone (DeRoy, 1), 7α-acetoxy-6β-hydroxyroyleanone (Roy, 2), and Parvifloron D (ParvD, 3) were obtained from Plectranthus spp. and showed promising biological activities, such as cytotoxicity. The inhibitory effects of the different natural abietanes (1-3) were compared in MFC7, SkBr3, and SUM159 cell lines, as well as SUM159 grown in cancer stem cell-inducing conditions. Based on the royleanones’ bioactivity, the derivatives RoyBz (4), RoyBzCl (5), RoyPr2 (6), and DihydroxyRoy (7), previously obtained from 2, were selected for further studies. Protein kinases C (PKCs) are involved in several carcinogenic processes. Thus, PKCs are potential targets for cancer therapy. To date, the portfolio of available PKC modulators remains very limited due to the difficulty of designing isozyme-selective PKC modulators. As such, molecular docking was used to evaluate royleanones 1-6 as predicted isozyme-selective PKC binders. Subtle changes in the binding site of each PKC isoform change the predicted interaction profiles of the ligands. Subtle changes in royleanone substitution patterns, such as a double substitution only with non-substituted phenyls, or hydroxybenzoate at position four that flips the binding mode of ParvD (3), can increase the predicted interactions in certain PKC subtypes., Plants have been used for centuries to treat several illnesses. The Plectranthus genus has a vast variety of species that has allowed the isolation of cytotoxic compounds with notable activities. The abietane diterpenes 6,7-dehydroroyleanone (DeRoy, 1), 7α-acetoxy-6β-hydroxyroyleanone (Roy, 2), and Parvifloron D (ParvD, 3) were obtained from Plectranthus spp. and showed promising biological activities, such as cytotoxicity. The inhibitory effects of the different natural abietanes (1-3) were compared in MFC7, SkBr3, and SUM159 cell lines, as well as SUM159 grown in cancer stem cell-inducing conditions. Based on the royleanones’ bioactivity, the derivatives RoyBz (4), RoyBzCl (5), RoyPr2 (6), and DihydroxyRoy (7), previously obtained from 2, were selected for further studies. Protein kinases C (PKCs) are involved in several carcinogenic processes. Thus, PKCs are potential targets for cancer therapy. To date, the portfolio of available PKC modulators remains very limited due to the difficulty of designing isozyme-selective PKC modulators. As such, molecular docking was used to evaluate royleanones 1-6 as predicted isozyme-selective PKC binders. Subtle changes in the binding site of each PKC isoform change the predicted interaction profiles of the ligands. Subtle changes in royleanone substitution patterns, such as a double substitution only with non-substituted phenyls, or hydroxybenzoate at position four that flips the binding mode of ParvD (3), can increase the predicted interactions in certain PKC subtypes.",
journal = "International Journal of Molecular Sciences",
title = "Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones",
volume = "21",
number = "10",
pages = "3671",
doi = "10.3390/ijms21103671"
}

Isca, V. M. S., Senćanski, M. V., Filipović, N. R., Dos Santos, D. J. V. A., Čipak Gašparović, A., Saraiva, L., Afonso, C. A. M., Rijo, P.,& Garcia-Sosa, A. T.. (2020). Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones. in International Journal of Molecular Sciences, 21(10), 3671.
https://doi.org/10.3390/ijms21103671

Isca VMS, Senćanski MV, Filipović NR, Dos Santos DJVA, Čipak Gašparović A, Saraiva L, Afonso CAM, Rijo P, Garcia-Sosa AT. Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones. in International Journal of Molecular Sciences. 2020;21(10):3671.
doi:10.3390/ijms21103671 .

Isca, Vera M. S., Senćanski, Milan V., Filipović, Nenad R., Dos Santos, Daniel J. V. A., Čipak Gašparović, Ana, Saraiva, Lucilia, Afonso, Carlos A M, Rijo, Patrícia, Garcia-Sosa, Alfonso T, "Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones" in International Journal of Molecular Sciences, 21, no. 10 (2020):3671,
https://doi.org/10.3390/ijms21103671 . .

TY  - JOUR
AU  - Bjelogrlić, Snežana K.
AU  - Todorović, Tamara
AU  - Kojić, Milan O.
AU  - Senćanski, Milan V.
AU  - Nikolić, Milan R.
AU  - Višnjevac, Aleksandar
AU  - Araškov, Jovana
AU  - Miljković, Marija S.
AU  - Muller, Christian D.
AU  - Filipović, Nenad R.
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8382
AB  - Anticancer activity of Pd complexes 1–5 with bidentate N-heteroaromatic hydrazone ligands was investigated on human acute monocytic leukemia (THP-1; cells in a suspension) and human mammary adenocarcinoma (MCF-7; two-dimensional layer and three-dimensional spheroid tumor model) cell lines. For the Pd(II) complexes with condensation products of ethyl hydrazainoacetate and quinoline-8-carboxaldehyde (complex 1) and 2-formylpyridine (complex 3), for which apoptosis was determined as a mechanism of anticancer activity, further investigation revealed that they arrest the cell cycle in G0/G1 phase, induce generation of reactive oxygen species and inhibit Topoisomerase I in vitro. In silico studies corroborate experimental findings that these complexes show topoisomerase inhibition activity in the micromolar range and indicate binding to a DNA's minor groove as another potential target. Based on the results obtained by circular dichroism and fluorescence spectroscopy measurements, the most active complexes are suitable to be delivered to a blood stream via human serum albumin.
T2  - Journal of Inorganic Biochemistry
T1  - Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification
VL  - 199
SP  - UNSP 110758
DO  - 10.1016/j.jinorgbio.2019.110758
ER  - 

@article{
author = "Bjelogrlić, Snežana K. and Todorović, Tamara and Kojić, Milan O. and Senćanski, Milan V. and Nikolić, Milan R. and Višnjevac, Aleksandar and Araškov, Jovana and Miljković, Marija S. and Muller, Christian D. and Filipović, Nenad R.",
year = "2019",
abstract = "Anticancer activity of Pd complexes 1–5 with bidentate N-heteroaromatic hydrazone ligands was investigated on human acute monocytic leukemia (THP-1; cells in a suspension) and human mammary adenocarcinoma (MCF-7; two-dimensional layer and three-dimensional spheroid tumor model) cell lines. For the Pd(II) complexes with condensation products of ethyl hydrazainoacetate and quinoline-8-carboxaldehyde (complex 1) and 2-formylpyridine (complex 3), for which apoptosis was determined as a mechanism of anticancer activity, further investigation revealed that they arrest the cell cycle in G0/G1 phase, induce generation of reactive oxygen species and inhibit Topoisomerase I in vitro. In silico studies corroborate experimental findings that these complexes show topoisomerase inhibition activity in the micromolar range and indicate binding to a DNA's minor groove as another potential target. Based on the results obtained by circular dichroism and fluorescence spectroscopy measurements, the most active complexes are suitable to be delivered to a blood stream via human serum albumin.",
journal = "Journal of Inorganic Biochemistry",
title = "Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification",
volume = "199",
pages = "UNSP 110758",
doi = "10.1016/j.jinorgbio.2019.110758"
}

Bjelogrlić, S. K., Todorović, T., Kojić, M. O., Senćanski, M. V., Nikolić, M. R., Višnjevac, A., Araškov, J., Miljković, M. S., Muller, C. D.,& Filipović, N. R.. (2019). Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification. in Journal of Inorganic Biochemistry, 199, UNSP 110758.
https://doi.org/10.1016/j.jinorgbio.2019.110758

Bjelogrlić SK, Todorović T, Kojić MO, Senćanski MV, Nikolić MR, Višnjevac A, Araškov J, Miljković MS, Muller CD, Filipović NR. Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification. in Journal of Inorganic Biochemistry. 2019;199:UNSP 110758.
doi:10.1016/j.jinorgbio.2019.110758 .

Bjelogrlić, Snežana K., Todorović, Tamara, Kojić, Milan O., Senćanski, Milan V., Nikolić, Milan R., Višnjevac, Aleksandar, Araškov, Jovana, Miljković, Marija S., Muller, Christian D., Filipović, Nenad R., "Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification" in Journal of Inorganic Biochemistry, 199 (2019):UNSP 110758,
https://doi.org/10.1016/j.jinorgbio.2019.110758 . .