The Experts below are selected from a list of 114 Experts worldwide ranked by ideXlab platform
Paolo Lombardi - One of the best experts on this subject based on the ideXlab platform.
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pyridine Derivative of the natural alkaloid Berberine as human telomeric g4 dna binder a solution and solid state study
ACS Medicinal Chemistry Letters, 2020Co-Authors: Francesco Papi, Paolo Lombardi, Carla Bazzicalupi, M Ferraroni, Giulia Ciolli, Asma Yasmeen Khan, Gopinatha Suresh Kumar, Paola GratteriAbstract:Telomerase is an enzyme deputed to the maintenance of eukaryotic chromosomes; however, its overexpression is a recognized hallmark of many cancer forms. A viable route for the inhibition of telomerase in malignant cells is the stabilization of G-quadruplex structures (G4) at the 3′ overhang of telomeres. Berberine has shown in this regard valuable G4 binding properties together with a significant anticancer activity and telomerase inhibition effects. Here, we focused on a Berberine Derivative featuring a pyridine containing side group at the 13th position. Such modification actually improves the binding toward telomeric G-quadruplexes and establishes a degree of selectivity in the interaction with different sequences. Moreover, the X-ray crystal structure obtained for the complex formed by the ligand and a bimolecular human telomeric quadruplex affords a better understanding of the 13-Berberine Derivatives behavior with telomeric G4 and allows to draw useful insights for the future design of Derivatives w...
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pyridine Derivative of the natural alkaloid Berberine as human telomeric g4 dna binder a solution and solid state study
ACS Medicinal Chemistry Letters, 2020Co-Authors: Francesco Papi, Paolo Lombardi, Carla Bazzicalupi, M Ferraroni, Giulia Ciolli, Asma Yasmeen Khan, Gopinatha Suresh Kumar, Paola GratteriAbstract:Telomerase is an enzyme deputed to the maintenance of eukaryotic chromosomes; however, its overexpression is a recognized hallmark of many cancer forms. A viable route for the inhibition of telomerase in malignant cells is the stabilization of G-quadruplex structures (G4) at the 3' overhang of telomeres. Berberine has shown in this regard valuable G4 binding properties together with a significant anticancer activity and telomerase inhibition effects. Here, we focused on a Berberine Derivative featuring a pyridine containing side group at the 13th position. Such modification actually improves the binding toward telomeric G-quadruplexes and establishes a degree of selectivity in the interaction with different sequences. Moreover, the X-ray crystal structure obtained for the complex formed by the ligand and a bimolecular human telomeric quadruplex affords a better understanding of the 13-Berberine Derivatives behavior with telomeric G4 and allows to draw useful insights for the future design of Derivatives with remarkable anticancer properties.
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antitumor activity of nax060 a novel semisynthetic Berberine Derivative in breast cancer cells
Biofactors, 2018Co-Authors: Elisa Pierpaoli, Paolo Lombardi, Carmela Salvatore, Cristina Geroni, Gaetano Fiorillo, Francesco Piacenza, Mauro ProvincialiAbstract:Breast cancer (BC) is the most common malignancy and the most common cause of cancer death in elderly women. We recently demonstrated that innovative compounds structurally related to and semisynthetically derived from the plant alkaloid Berberine represent a promising unexplored resource for novel therapeutic tools in BC therapy. In this study, we analyzed the effectiveness of new 13-dichlorophenylalkyl Berberine semisynthetic Derivatives (NAX060, NAX103, NAX111, and NAX114) on the viability of BC cell lines. Our results demonstrated that the new compounds effectively inhibited the growth of a variety of human BC cell lines. In particular, the viability of HER-2 overexpressing SK-BR-3 cells was significantly reduced by the treatment with NAX060, the most active compound, in a dose and time-dependent manner. In the same tumor cell line, NAX060 induced a strong increase in sub-G1 population while G0/G1 and G2/M phase cells remarkably decreased. NAX060 withdrawal after 72 h of treatment resulted in an irreversible cell proliferation arrest and increasing cell death. Real-time PCR analyses showed that NAX060 induced the expression of some cell-cycle checkpoint molecules involved in cell senescence such as p21WAF1, p27, p16INK4a, and PAI-1. Furthermore, the HER-2 protein expression and phosphorylation, as well as the level of heparanase expression, were remarkably reduced on SK-BR-3 cells. NAX060 was effective also on HER-2 negative tumor cells, and, in particular, on human triple-negative MDA-MB-231 cells. These data suggest a potential therapeutic effect of NAX060 compound in the management of BC malignancies. Interestingly, NAX060 may represent a new useful tool also in triple-negative BC. © 2018 BioFactors, 44(5):443-452, 2018.
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doi:10.1093/carcin/bgv103 Original Manuscript
2016Co-Authors: Elisa Pierpaoli, Elisa Damiani, Fiorenza Orl, Guendalina Lucarini, Beatrice Bartozzi, Paolo Lombardi, Carmela Salvatore, Cristina Geroni, Abele DonatiAbstract:original manuscript Antiangiogenic and antitumor activities of Berberine Derivative NAX014 compound in a transgenic murine model of HER2/neu-positive mammary carcinom
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antiangiogenic and antitumor activities of Berberine Derivative nax014 compound in a transgenic murine model of her2 neu positive mammary carcinoma
Carcinogenesis, 2015Co-Authors: Elisa Pierpaoli, Elisa Damiani, Guendalina Lucarini, Beatrice Bartozzi, Paolo Lombardi, Carmela Salvatore, Cristina Geroni, Abele Donati, Fiorenza Orlando, Mauro ProvincialiAbstract:Berberine (BBR) is a natural isoquinoline alkaloid with proven antiangiogenic and anticancer activities. We recently demonstrated that BBR and its synthetic Derivative 13-(4-chlorophenylethyl)Berberine iodide, NAX014, exert antiproliferative activity against HER2-overexpressing breast cancer cells, inducing apoptosis, modulating the expression of cell cycle checkpoint molecules involved in cell senescence, and reducing both HER2 expression and phosphorylation on tumor cells. In this study, we examined the anticancer properties of BBR and NAX014 in a transgenic mouse model which spontaneously develops HER2-positive mammary tumors. Repeated intraperitoneal injections of a safety dose (2.5mg/kg) of NAX014 delayed the development of tumors, reducing both the number and size of tumor masses. In vivo sidestream dark field videomicroscopy revealed a significant lower vessel density in mammary tumors from NAX014-treated mice in comparison with the control group. Immunohistochemical evaluation using CD34 antibody confirmed the reduced vessel density in NAX014 group. Statistically significant increase of senescence associated β-galactosidase and p16 expression, and reduced expression of heparanase were observed in tumors from NAX014-treated mice than in tumors from control animals. Finally, NAX014 treatment decreased the level of perforine and granzyme mRNA in mammary tumors. Berberine did not show any statistically significant modulation in comparison with control mice. The results of the present study indicate that NAX014 is more effective than BBR in exerting anticancer activity delaying the development of mammary tumors in mice transgenic for the HER-2/neu oncogene. The antitumor efficacy of NAX014 is mainly related to its effect on tumor vascular network and on induction of tumor cell senescence.
Paola Gratteri - One of the best experts on this subject based on the ideXlab platform.
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pyridine Derivative of the natural alkaloid Berberine as human telomeric g4 dna binder a solution and solid state study
ACS Medicinal Chemistry Letters, 2020Co-Authors: Francesco Papi, Paolo Lombardi, Carla Bazzicalupi, M Ferraroni, Giulia Ciolli, Asma Yasmeen Khan, Gopinatha Suresh Kumar, Paola GratteriAbstract:Telomerase is an enzyme deputed to the maintenance of eukaryotic chromosomes; however, its overexpression is a recognized hallmark of many cancer forms. A viable route for the inhibition of telomerase in malignant cells is the stabilization of G-quadruplex structures (G4) at the 3′ overhang of telomeres. Berberine has shown in this regard valuable G4 binding properties together with a significant anticancer activity and telomerase inhibition effects. Here, we focused on a Berberine Derivative featuring a pyridine containing side group at the 13th position. Such modification actually improves the binding toward telomeric G-quadruplexes and establishes a degree of selectivity in the interaction with different sequences. Moreover, the X-ray crystal structure obtained for the complex formed by the ligand and a bimolecular human telomeric quadruplex affords a better understanding of the 13-Berberine Derivatives behavior with telomeric G4 and allows to draw useful insights for the future design of Derivatives w...
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pyridine Derivative of the natural alkaloid Berberine as human telomeric g4 dna binder a solution and solid state study
ACS Medicinal Chemistry Letters, 2020Co-Authors: Francesco Papi, Paolo Lombardi, Carla Bazzicalupi, M Ferraroni, Giulia Ciolli, Asma Yasmeen Khan, Gopinatha Suresh Kumar, Paola GratteriAbstract:Telomerase is an enzyme deputed to the maintenance of eukaryotic chromosomes; however, its overexpression is a recognized hallmark of many cancer forms. A viable route for the inhibition of telomerase in malignant cells is the stabilization of G-quadruplex structures (G4) at the 3' overhang of telomeres. Berberine has shown in this regard valuable G4 binding properties together with a significant anticancer activity and telomerase inhibition effects. Here, we focused on a Berberine Derivative featuring a pyridine containing side group at the 13th position. Such modification actually improves the binding toward telomeric G-quadruplexes and establishes a degree of selectivity in the interaction with different sequences. Moreover, the X-ray crystal structure obtained for the complex formed by the ligand and a bimolecular human telomeric quadruplex affords a better understanding of the 13-Berberine Derivatives behavior with telomeric G4 and allows to draw useful insights for the future design of Derivatives with remarkable anticancer properties.
Elisa Pierpaoli - One of the best experts on this subject based on the ideXlab platform.
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antitumor activity of nax060 a novel semisynthetic Berberine Derivative in breast cancer cells
Biofactors, 2018Co-Authors: Elisa Pierpaoli, Paolo Lombardi, Carmela Salvatore, Cristina Geroni, Gaetano Fiorillo, Francesco Piacenza, Mauro ProvincialiAbstract:Breast cancer (BC) is the most common malignancy and the most common cause of cancer death in elderly women. We recently demonstrated that innovative compounds structurally related to and semisynthetically derived from the plant alkaloid Berberine represent a promising unexplored resource for novel therapeutic tools in BC therapy. In this study, we analyzed the effectiveness of new 13-dichlorophenylalkyl Berberine semisynthetic Derivatives (NAX060, NAX103, NAX111, and NAX114) on the viability of BC cell lines. Our results demonstrated that the new compounds effectively inhibited the growth of a variety of human BC cell lines. In particular, the viability of HER-2 overexpressing SK-BR-3 cells was significantly reduced by the treatment with NAX060, the most active compound, in a dose and time-dependent manner. In the same tumor cell line, NAX060 induced a strong increase in sub-G1 population while G0/G1 and G2/M phase cells remarkably decreased. NAX060 withdrawal after 72 h of treatment resulted in an irreversible cell proliferation arrest and increasing cell death. Real-time PCR analyses showed that NAX060 induced the expression of some cell-cycle checkpoint molecules involved in cell senescence such as p21WAF1, p27, p16INK4a, and PAI-1. Furthermore, the HER-2 protein expression and phosphorylation, as well as the level of heparanase expression, were remarkably reduced on SK-BR-3 cells. NAX060 was effective also on HER-2 negative tumor cells, and, in particular, on human triple-negative MDA-MB-231 cells. These data suggest a potential therapeutic effect of NAX060 compound in the management of BC malignancies. Interestingly, NAX060 may represent a new useful tool also in triple-negative BC. © 2018 BioFactors, 44(5):443-452, 2018.
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doi:10.1093/carcin/bgv103 Original Manuscript
2016Co-Authors: Elisa Pierpaoli, Elisa Damiani, Fiorenza Orl, Guendalina Lucarini, Beatrice Bartozzi, Paolo Lombardi, Carmela Salvatore, Cristina Geroni, Abele DonatiAbstract:original manuscript Antiangiogenic and antitumor activities of Berberine Derivative NAX014 compound in a transgenic murine model of HER2/neu-positive mammary carcinom
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antiangiogenic and antitumor activities of Berberine Derivative nax014 compound in a transgenic murine model of her2 neu positive mammary carcinoma
Carcinogenesis, 2015Co-Authors: Elisa Pierpaoli, Elisa Damiani, Guendalina Lucarini, Beatrice Bartozzi, Paolo Lombardi, Carmela Salvatore, Cristina Geroni, Abele Donati, Fiorenza Orlando, Mauro ProvincialiAbstract:Berberine (BBR) is a natural isoquinoline alkaloid with proven antiangiogenic and anticancer activities. We recently demonstrated that BBR and its synthetic Derivative 13-(4-chlorophenylethyl)Berberine iodide, NAX014, exert antiproliferative activity against HER2-overexpressing breast cancer cells, inducing apoptosis, modulating the expression of cell cycle checkpoint molecules involved in cell senescence, and reducing both HER2 expression and phosphorylation on tumor cells. In this study, we examined the anticancer properties of BBR and NAX014 in a transgenic mouse model which spontaneously develops HER2-positive mammary tumors. Repeated intraperitoneal injections of a safety dose (2.5mg/kg) of NAX014 delayed the development of tumors, reducing both the number and size of tumor masses. In vivo sidestream dark field videomicroscopy revealed a significant lower vessel density in mammary tumors from NAX014-treated mice in comparison with the control group. Immunohistochemical evaluation using CD34 antibody confirmed the reduced vessel density in NAX014 group. Statistically significant increase of senescence associated β-galactosidase and p16 expression, and reduced expression of heparanase were observed in tumors from NAX014-treated mice than in tumors from control animals. Finally, NAX014 treatment decreased the level of perforine and granzyme mRNA in mammary tumors. Berberine did not show any statistically significant modulation in comparison with control mice. The results of the present study indicate that NAX014 is more effective than BBR in exerting anticancer activity delaying the development of mammary tumors in mice transgenic for the HER-2/neu oncogene. The antitumor efficacy of NAX014 is mainly related to its effect on tumor vascular network and on induction of tumor cell senescence.
Mauro Provinciali - One of the best experts on this subject based on the ideXlab platform.
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antitumor activity of nax060 a novel semisynthetic Berberine Derivative in breast cancer cells
Biofactors, 2018Co-Authors: Elisa Pierpaoli, Paolo Lombardi, Carmela Salvatore, Cristina Geroni, Gaetano Fiorillo, Francesco Piacenza, Mauro ProvincialiAbstract:Breast cancer (BC) is the most common malignancy and the most common cause of cancer death in elderly women. We recently demonstrated that innovative compounds structurally related to and semisynthetically derived from the plant alkaloid Berberine represent a promising unexplored resource for novel therapeutic tools in BC therapy. In this study, we analyzed the effectiveness of new 13-dichlorophenylalkyl Berberine semisynthetic Derivatives (NAX060, NAX103, NAX111, and NAX114) on the viability of BC cell lines. Our results demonstrated that the new compounds effectively inhibited the growth of a variety of human BC cell lines. In particular, the viability of HER-2 overexpressing SK-BR-3 cells was significantly reduced by the treatment with NAX060, the most active compound, in a dose and time-dependent manner. In the same tumor cell line, NAX060 induced a strong increase in sub-G1 population while G0/G1 and G2/M phase cells remarkably decreased. NAX060 withdrawal after 72 h of treatment resulted in an irreversible cell proliferation arrest and increasing cell death. Real-time PCR analyses showed that NAX060 induced the expression of some cell-cycle checkpoint molecules involved in cell senescence such as p21WAF1, p27, p16INK4a, and PAI-1. Furthermore, the HER-2 protein expression and phosphorylation, as well as the level of heparanase expression, were remarkably reduced on SK-BR-3 cells. NAX060 was effective also on HER-2 negative tumor cells, and, in particular, on human triple-negative MDA-MB-231 cells. These data suggest a potential therapeutic effect of NAX060 compound in the management of BC malignancies. Interestingly, NAX060 may represent a new useful tool also in triple-negative BC. © 2018 BioFactors, 44(5):443-452, 2018.
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antiangiogenic and antitumor activities of Berberine Derivative nax014 compound in a transgenic murine model of her2 neu positive mammary carcinoma
Carcinogenesis, 2015Co-Authors: Elisa Pierpaoli, Elisa Damiani, Guendalina Lucarini, Beatrice Bartozzi, Paolo Lombardi, Carmela Salvatore, Cristina Geroni, Abele Donati, Fiorenza Orlando, Mauro ProvincialiAbstract:Berberine (BBR) is a natural isoquinoline alkaloid with proven antiangiogenic and anticancer activities. We recently demonstrated that BBR and its synthetic Derivative 13-(4-chlorophenylethyl)Berberine iodide, NAX014, exert antiproliferative activity against HER2-overexpressing breast cancer cells, inducing apoptosis, modulating the expression of cell cycle checkpoint molecules involved in cell senescence, and reducing both HER2 expression and phosphorylation on tumor cells. In this study, we examined the anticancer properties of BBR and NAX014 in a transgenic mouse model which spontaneously develops HER2-positive mammary tumors. Repeated intraperitoneal injections of a safety dose (2.5mg/kg) of NAX014 delayed the development of tumors, reducing both the number and size of tumor masses. In vivo sidestream dark field videomicroscopy revealed a significant lower vessel density in mammary tumors from NAX014-treated mice in comparison with the control group. Immunohistochemical evaluation using CD34 antibody confirmed the reduced vessel density in NAX014 group. Statistically significant increase of senescence associated β-galactosidase and p16 expression, and reduced expression of heparanase were observed in tumors from NAX014-treated mice than in tumors from control animals. Finally, NAX014 treatment decreased the level of perforine and granzyme mRNA in mammary tumors. Berberine did not show any statistically significant modulation in comparison with control mice. The results of the present study indicate that NAX014 is more effective than BBR in exerting anticancer activity delaying the development of mammary tumors in mice transgenic for the HER-2/neu oncogene. The antitumor efficacy of NAX014 is mainly related to its effect on tumor vascular network and on induction of tumor cell senescence.
Francesco Papi - One of the best experts on this subject based on the ideXlab platform.
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pyridine Derivative of the natural alkaloid Berberine as human telomeric g4 dna binder a solution and solid state study
ACS Medicinal Chemistry Letters, 2020Co-Authors: Francesco Papi, Paolo Lombardi, Carla Bazzicalupi, M Ferraroni, Giulia Ciolli, Asma Yasmeen Khan, Gopinatha Suresh Kumar, Paola GratteriAbstract:Telomerase is an enzyme deputed to the maintenance of eukaryotic chromosomes; however, its overexpression is a recognized hallmark of many cancer forms. A viable route for the inhibition of telomerase in malignant cells is the stabilization of G-quadruplex structures (G4) at the 3′ overhang of telomeres. Berberine has shown in this regard valuable G4 binding properties together with a significant anticancer activity and telomerase inhibition effects. Here, we focused on a Berberine Derivative featuring a pyridine containing side group at the 13th position. Such modification actually improves the binding toward telomeric G-quadruplexes and establishes a degree of selectivity in the interaction with different sequences. Moreover, the X-ray crystal structure obtained for the complex formed by the ligand and a bimolecular human telomeric quadruplex affords a better understanding of the 13-Berberine Derivatives behavior with telomeric G4 and allows to draw useful insights for the future design of Derivatives w...
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pyridine Derivative of the natural alkaloid Berberine as human telomeric g4 dna binder a solution and solid state study
ACS Medicinal Chemistry Letters, 2020Co-Authors: Francesco Papi, Paolo Lombardi, Carla Bazzicalupi, M Ferraroni, Giulia Ciolli, Asma Yasmeen Khan, Gopinatha Suresh Kumar, Paola GratteriAbstract:Telomerase is an enzyme deputed to the maintenance of eukaryotic chromosomes; however, its overexpression is a recognized hallmark of many cancer forms. A viable route for the inhibition of telomerase in malignant cells is the stabilization of G-quadruplex structures (G4) at the 3' overhang of telomeres. Berberine has shown in this regard valuable G4 binding properties together with a significant anticancer activity and telomerase inhibition effects. Here, we focused on a Berberine Derivative featuring a pyridine containing side group at the 13th position. Such modification actually improves the binding toward telomeric G-quadruplexes and establishes a degree of selectivity in the interaction with different sequences. Moreover, the X-ray crystal structure obtained for the complex formed by the ligand and a bimolecular human telomeric quadruplex affords a better understanding of the 13-Berberine Derivatives behavior with telomeric G4 and allows to draw useful insights for the future design of Derivatives with remarkable anticancer properties.