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Papers by Ana Isabel Tomaz

Research paper thumbnail of INOR 381-Analyzing vanadium nuclease activity by plasmid electrophoresis

Research paper thumbnail of Ruthenium(II) Polypyridyl Complexes with Benzothiophene and Benzimidazole Derivatives: Synthesis, Antitumor Activity, Solution Studies and Biospeciation

Research paper thumbnail of New ternary Fe(III)-8-hydroxyquinoline–reduced Schiff base complexes as selective anticancer drug candidates

Journal of Inorganic Biochemistry

Research paper thumbnail of Ruthenium and iron metallodrugs: new inorganic and organometallic complexes as prospective anticancer agents

Synthetic Inorganic Chemistry

Abstract In this chapter we address the development of ruthenium- and iron-based metallodrugs as ... more Abstract In this chapter we address the development of ruthenium- and iron-based metallodrugs as prospective chemotherapeutics in cancer treatment. We provide an overview of the field addressing iron and ruthenium complexes reported as promising anticancer metallodrug candidates, their properties and specific features, and mostly focus on newer contributions in this field (including synthetic routes often followed), which include “classical” coordination complexes and organometallic compounds. The first group comprises Fe(III) and Ru(III) complexes with octahedral geometry and a tetradentate ligand, namely ternary tripodal aminobisphenolates and cyclam derivatives for Fe(III) or salen- and salan-like ligands for Ru(III). In the larger group of organometallic complexes, we highlight the value of the “M(Cp)” scaffold in metallodrug design (M being Ru(II) and Fe(II), and Cp being η5-cyclopentadienyl) and provide examples of very effective compounds with modes of action that are distinct from those of Pt-based drugs in clinical use, including some “Ru(Cp)” complexes with the ability to overcome multidrug resistance mechanisms.

Research paper thumbnail of CCDC 2042408: Experimental Crystal Structure Determination

Research paper thumbnail of CCDC 2042412: Experimental Crystal Structure Determination

Research paper thumbnail of Novel silver(I) compounds display strong activity towards resistant ovarian and colorectal cancer cell lines

Proceedings of 7th International Electronic Conference on Medicinal Chemistry, 2021

Carboplatin (CBP) is used to treat several types of cancers including ovarian carcinoma (OC). How... more Carboplatin (CBP) is used to treat several types of cancers including ovarian carcinoma (OC). However, drug resistance is a frequent obstacle for successful treatment. In the quest for new (metallo)drugs to treat OC with acquired resistance, we have explored the use of silver(I)-based compounds containing 2,2'-bipyridine derivatives and triphenylphosphane (PPh 3) or 1,2-bis(diphenylphosphino)ethane (dppe) co-ligands as prospective anticancer agents. Their cytotoxic activity was tested in two human OC models (SKOV-3 and MESOV),

Research paper thumbnail of Ruthenium organometallic compounds as ABC drug efflux-targeted agents and collateral sensitizers

Proceedings of 6th International Electronic Conference on Medicinal Chemistry, 2020

Research paper thumbnail of May iron(III) complexes containing phenanthroline derivatives as ligands be prospective anticancer agents?

European Journal of Medicinal Chemistry, 2019

May iron(III) complexes containing phenanthroline derivatives as ligands be prospective anticance... more May iron(III) complexes containing phenanthroline derivatives as ligands be prospective anticancer agents?,

Research paper thumbnail of Screening organometallic binuclear thiosemicarbazone ruthenium complexes as potential anti-tumour agents: cytotoxic activity and human serum albumin binding mechanism

Dalton Transactions, 2013

Supporting Information includes the following Sections: 1. Cell Studies with figures SI.1-In vitr... more Supporting Information includes the following Sections: 1. Cell Studies with figures SI.1-In vitro cytotoxic activity of ligands L1-L4 against A2780, MCF7 and PC3 cell lines; SI.2-In vitro cytotoxic activity of the thiosemicarbazone (TSC) ligands; SI.3-Dose-response profiles of cell viability in A2780, MCF7 and PC3 cell lines; 2. Time-dependent induced CD spectra for HSA binding of complexes 1 and 4 with explaining text, and figures SI.4-Binding of complex 1 to HSA monitored by CD spectroscopy (time dependence and equilibrium conditions); SI.5-Time dependence of binding of complex 4 to HSA; SI.6-UV-Visible spectra on time dependence of complex 4 binding to HSA. 3. Mechanism of Förster Resonance Energy Transfer (FRET) for the HSA-complex 4 system SI.7-Spectral overlap of the HSA fluorescence emission and complex 4 absorbtion.

Research paper thumbnail of CCDC 2042410: Experimental Crystal Structure Determination

Research paper thumbnail of The system VO 2++oxidized glutathione: a potentiometric and spectroscopic study

Journal of Inorganic Biochemistry, 2001

The equilibria in the system VO2++oxidized glutathione in aqueous solution have been studied in t... more The equilibria in the system VO2++oxidized glutathione in aqueous solution have been studied in the pH range 2–11 by a combination of pH potentiometry and spectroscopy (EPR, visible absorption and circular dichroism). The results of the various methods are self-consistent and the equilibrium model includes the species MLH4, MLH3, MLH2, MLH, ML, MLH−1, MLH−2 and several hydrolysis products (where H4L

Research paper thumbnail of Electronic Properties of a Cytosine Decavanadate: Toward a Better Understanding of Chemical and Biological Properties of Decavanadates

Inorganic …, 2009

We have synthesized and crystallized a cytosine-decavanadate compound, Na(3) [V(10)O(28)] (C(4)N(... more We have synthesized and crystallized a cytosine-decavanadate compound, Na(3) [V(10)O(28)] (C(4)N(3)OH(5))(3)(C(4)N(3)OH(6))(3).10H(2)O, and its crystal structure has been determined from a single-crystal X-ray diffraction. A high resolution X-ray diffraction experiment at 210 K (in P1 space group phase) was carried out. The data were refined using a pseudo-atom multipole model to get the electron density and the electrostatic properties of the decavanadate-cytosine complex. Static deformation density maps and Atoms in Molecules (AIM) topological analysis were used for this purpose. To get insight into the reactivity of the decavanadate anion, we have determined the atomic net charges and the molecular electrostatic potential. Special attention was paid to the hydrogen bonding occurring in the solid state between the decavanadate anion and its environment. The comparison of the experimental electronic characteristics of the decavanadate anions to those found in literature reveals that this anion is a rigid entity conserving its intrinsic properties. This is of particular importance for the future investigations of the biological activities of the decavanadate anion.

Research paper thumbnail of {"__content__"=>"Ru( p-cymene) Compounds as Effective and Selective Anticancer Candidates with No Toxicity in Vivo.", "sup"=>{"__content__"=>"II"}}

Inorganic chemistry, Jan 19, 2018

Ruthenium(II) complexes are currently considered a viable alternative to the widely used platinum... more Ruthenium(II) complexes are currently considered a viable alternative to the widely used platinum complexes as efficient anticancer agents. We herein present the synthesis and characterization of half-sandwich ruthenium compounds with the general formula [Ru( p-cymene)(L-N,N)Cl][CFSO] (L = 3,6-di-2-pyridyl-1,2,4,5-tetrazine (1) 6,7-dimethyl-2,3-bis(pyridin-2-yl)quinoxaline (2)), which have been synthesized by substitution reactions from the precursor dimer [Ru( p-cymene)(Cl)(μ-Cl)] and were characterized by elemental analysis, mass spectrometry, H NMR, UV-vis, and IR spectroscopy, conductivity measurements, and cyclic voltammetry. The molecular structure for complex 2 was determined by single-crystal X-ray diffraction. The cytotoxic activity of these compounds was evaluated against human tumor cells, namely ovarian carcinoma A2780 and breast MCF7 and MDAMB231 adenocarcinoma cells, and against normal primary fibroblasts. Whereas the cytotoxic activity of 1 is moderate, IC values foun...

Research paper thumbnail of Interaction and lipid-induced conformation of two cecropin-melittin hybrid peptides depend on peptide and membrane composition

The Journal of …, 2005

The interaction of two hybrid peptides of cecropin A and melittin [CA(1-8)M(1-18) and CA(1-7)M(2-... more The interaction of two hybrid peptides of cecropin A and melittin [CA(1-8)M(1-18) and CA(1-7)M(2-9)] with liposomes was studied by differential scanning calorimetry (DSC), circular dichroism (CD), and quasi-elastic light scattering (QELS). The study was carried out with large unilamellar vesicles (LUVs) of three different lipid compositions: 1,2-dimyristoil-sn-glycero-3-phosphocholine (DMPC), 1,2-dimyristoylsn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and a binary mixture of DMPC/DMPG, in a wide range of peptide-to-lipid (P:L) molar ratios (0 to 1:7). DSC results indicate that, for both peptides, the interaction depends on membrane composition, with very different behavior for zwitterionic and anionic membranes. CD data show that, although the two peptides have different secondary structures in buffer (random coil for CA(1-7)M(2-9) and predominantly-sheet for CA(1-8)M(1-18)), they both adopt an R-helical structure in the presence of the membranes. Overall, results are compatible with a model involving a strong electrostatic surface interaction between the peptides and the negatively charged liposomes, which gives place to aggregation in the gel phase and precipitation after a threshold peptide concentration. In the case of zwitterionic membranes, a progressive surface coverage with peptide molecules destabilizes the membrane, eventually leading to membrane disruption. Moreover, delicate modulations in behavior were observed depending on the peptide.

Research paper thumbnail of Ruthenium-Based Anticancer Compounds: Insights into Their Cellular Targeting and Mechanism of Action

Research paper thumbnail of Half-Sandwich Ru(p-cymene) Compounds with Diphosphanes: In Vitro and In Vivo Evaluation As Potential Anticancer Metallodrugs

Research paper thumbnail of Unprecedented collateral sensitivity for cisplatin-resistant lung cancer cells presented by new ruthenium organometallic compounds

Inorganic Chemistry Frontiers

Ru compounds exhibit collateral sensitivity in cisplatin-resistant NSCLC and increase cisplatin a... more Ru compounds exhibit collateral sensitivity in cisplatin-resistant NSCLC and increase cisplatin activity by inhibiting efflux pumps.

Research paper thumbnail of Experimental Data on Novel Fe(Iii)-Complexes Containing Phenanthroline Derivatives for their Anticancer Properties

Research paper thumbnail of Interaction with Blood Proteins of a Ruthenium(II) Nitrofuryl Semicarbazone Complex: Effect on the Antitumoral Activity

Molecules

The steady rise in the cancer burden and grim statistics set a vital need for new therapeutic sol... more The steady rise in the cancer burden and grim statistics set a vital need for new therapeutic solutions. Given their high efficiency, metallodrugs are quite appealing in cancer chemotherapy. This work examined the anticancer activity of an anti-trypanosomal ruthenium-based compound bearing the 5-nitrofuryl pharmacophore, [RuII(dmso)2(5-nitro-2-furaldehyde semicarbazone)] (abbreviated as RuNTF; dmso is the dimethyl sulfoxide ligand). The cytotoxicity of RuNTF was evaluated in vitro against ovarian adenocarcinoma, hormone-dependent breast adenocarcinoma, prostate carcinoma (grade IV) and V79 lung fibroblasts human cells. The activity of RuNTF was similar to the benchmark metallodrug cisplatin for the breast line and inactive against the prostate line and lung fibroblasts. Given the known role of serum protein binding in drug bioavailability and the distribution via blood plasma, this study assessed the interaction of RuNTF with human serum albumin (HSA) by circular dichroism (CD) and ...

Research paper thumbnail of INOR 381-Analyzing vanadium nuclease activity by plasmid electrophoresis

Research paper thumbnail of Ruthenium(II) Polypyridyl Complexes with Benzothiophene and Benzimidazole Derivatives: Synthesis, Antitumor Activity, Solution Studies and Biospeciation

Research paper thumbnail of New ternary Fe(III)-8-hydroxyquinoline–reduced Schiff base complexes as selective anticancer drug candidates

Journal of Inorganic Biochemistry

Research paper thumbnail of Ruthenium and iron metallodrugs: new inorganic and organometallic complexes as prospective anticancer agents

Synthetic Inorganic Chemistry

Abstract In this chapter we address the development of ruthenium- and iron-based metallodrugs as ... more Abstract In this chapter we address the development of ruthenium- and iron-based metallodrugs as prospective chemotherapeutics in cancer treatment. We provide an overview of the field addressing iron and ruthenium complexes reported as promising anticancer metallodrug candidates, their properties and specific features, and mostly focus on newer contributions in this field (including synthetic routes often followed), which include “classical” coordination complexes and organometallic compounds. The first group comprises Fe(III) and Ru(III) complexes with octahedral geometry and a tetradentate ligand, namely ternary tripodal aminobisphenolates and cyclam derivatives for Fe(III) or salen- and salan-like ligands for Ru(III). In the larger group of organometallic complexes, we highlight the value of the “M(Cp)” scaffold in metallodrug design (M being Ru(II) and Fe(II), and Cp being η5-cyclopentadienyl) and provide examples of very effective compounds with modes of action that are distinct from those of Pt-based drugs in clinical use, including some “Ru(Cp)” complexes with the ability to overcome multidrug resistance mechanisms.

Research paper thumbnail of CCDC 2042408: Experimental Crystal Structure Determination

Research paper thumbnail of CCDC 2042412: Experimental Crystal Structure Determination

Research paper thumbnail of Novel silver(I) compounds display strong activity towards resistant ovarian and colorectal cancer cell lines

Proceedings of 7th International Electronic Conference on Medicinal Chemistry, 2021

Carboplatin (CBP) is used to treat several types of cancers including ovarian carcinoma (OC). How... more Carboplatin (CBP) is used to treat several types of cancers including ovarian carcinoma (OC). However, drug resistance is a frequent obstacle for successful treatment. In the quest for new (metallo)drugs to treat OC with acquired resistance, we have explored the use of silver(I)-based compounds containing 2,2'-bipyridine derivatives and triphenylphosphane (PPh 3) or 1,2-bis(diphenylphosphino)ethane (dppe) co-ligands as prospective anticancer agents. Their cytotoxic activity was tested in two human OC models (SKOV-3 and MESOV),

Research paper thumbnail of Ruthenium organometallic compounds as ABC drug efflux-targeted agents and collateral sensitizers

Proceedings of 6th International Electronic Conference on Medicinal Chemistry, 2020

Research paper thumbnail of May iron(III) complexes containing phenanthroline derivatives as ligands be prospective anticancer agents?

European Journal of Medicinal Chemistry, 2019

May iron(III) complexes containing phenanthroline derivatives as ligands be prospective anticance... more May iron(III) complexes containing phenanthroline derivatives as ligands be prospective anticancer agents?,

Research paper thumbnail of Screening organometallic binuclear thiosemicarbazone ruthenium complexes as potential anti-tumour agents: cytotoxic activity and human serum albumin binding mechanism

Dalton Transactions, 2013

Supporting Information includes the following Sections: 1. Cell Studies with figures SI.1-In vitr... more Supporting Information includes the following Sections: 1. Cell Studies with figures SI.1-In vitro cytotoxic activity of ligands L1-L4 against A2780, MCF7 and PC3 cell lines; SI.2-In vitro cytotoxic activity of the thiosemicarbazone (TSC) ligands; SI.3-Dose-response profiles of cell viability in A2780, MCF7 and PC3 cell lines; 2. Time-dependent induced CD spectra for HSA binding of complexes 1 and 4 with explaining text, and figures SI.4-Binding of complex 1 to HSA monitored by CD spectroscopy (time dependence and equilibrium conditions); SI.5-Time dependence of binding of complex 4 to HSA; SI.6-UV-Visible spectra on time dependence of complex 4 binding to HSA. 3. Mechanism of Förster Resonance Energy Transfer (FRET) for the HSA-complex 4 system SI.7-Spectral overlap of the HSA fluorescence emission and complex 4 absorbtion.

Research paper thumbnail of CCDC 2042410: Experimental Crystal Structure Determination

Research paper thumbnail of The system VO 2++oxidized glutathione: a potentiometric and spectroscopic study

Journal of Inorganic Biochemistry, 2001

The equilibria in the system VO2++oxidized glutathione in aqueous solution have been studied in t... more The equilibria in the system VO2++oxidized glutathione in aqueous solution have been studied in the pH range 2–11 by a combination of pH potentiometry and spectroscopy (EPR, visible absorption and circular dichroism). The results of the various methods are self-consistent and the equilibrium model includes the species MLH4, MLH3, MLH2, MLH, ML, MLH−1, MLH−2 and several hydrolysis products (where H4L

Research paper thumbnail of Electronic Properties of a Cytosine Decavanadate: Toward a Better Understanding of Chemical and Biological Properties of Decavanadates

Inorganic …, 2009

We have synthesized and crystallized a cytosine-decavanadate compound, Na(3) [V(10)O(28)] (C(4)N(... more We have synthesized and crystallized a cytosine-decavanadate compound, Na(3) [V(10)O(28)] (C(4)N(3)OH(5))(3)(C(4)N(3)OH(6))(3).10H(2)O, and its crystal structure has been determined from a single-crystal X-ray diffraction. A high resolution X-ray diffraction experiment at 210 K (in P1 space group phase) was carried out. The data were refined using a pseudo-atom multipole model to get the electron density and the electrostatic properties of the decavanadate-cytosine complex. Static deformation density maps and Atoms in Molecules (AIM) topological analysis were used for this purpose. To get insight into the reactivity of the decavanadate anion, we have determined the atomic net charges and the molecular electrostatic potential. Special attention was paid to the hydrogen bonding occurring in the solid state between the decavanadate anion and its environment. The comparison of the experimental electronic characteristics of the decavanadate anions to those found in literature reveals that this anion is a rigid entity conserving its intrinsic properties. This is of particular importance for the future investigations of the biological activities of the decavanadate anion.

Research paper thumbnail of {"__content__"=>"Ru( p-cymene) Compounds as Effective and Selective Anticancer Candidates with No Toxicity in Vivo.", "sup"=>{"__content__"=>"II"}}

Inorganic chemistry, Jan 19, 2018

Ruthenium(II) complexes are currently considered a viable alternative to the widely used platinum... more Ruthenium(II) complexes are currently considered a viable alternative to the widely used platinum complexes as efficient anticancer agents. We herein present the synthesis and characterization of half-sandwich ruthenium compounds with the general formula [Ru( p-cymene)(L-N,N)Cl][CFSO] (L = 3,6-di-2-pyridyl-1,2,4,5-tetrazine (1) 6,7-dimethyl-2,3-bis(pyridin-2-yl)quinoxaline (2)), which have been synthesized by substitution reactions from the precursor dimer [Ru( p-cymene)(Cl)(μ-Cl)] and were characterized by elemental analysis, mass spectrometry, H NMR, UV-vis, and IR spectroscopy, conductivity measurements, and cyclic voltammetry. The molecular structure for complex 2 was determined by single-crystal X-ray diffraction. The cytotoxic activity of these compounds was evaluated against human tumor cells, namely ovarian carcinoma A2780 and breast MCF7 and MDAMB231 adenocarcinoma cells, and against normal primary fibroblasts. Whereas the cytotoxic activity of 1 is moderate, IC values foun...

Research paper thumbnail of Interaction and lipid-induced conformation of two cecropin-melittin hybrid peptides depend on peptide and membrane composition

The Journal of …, 2005

The interaction of two hybrid peptides of cecropin A and melittin [CA(1-8)M(1-18) and CA(1-7)M(2-... more The interaction of two hybrid peptides of cecropin A and melittin [CA(1-8)M(1-18) and CA(1-7)M(2-9)] with liposomes was studied by differential scanning calorimetry (DSC), circular dichroism (CD), and quasi-elastic light scattering (QELS). The study was carried out with large unilamellar vesicles (LUVs) of three different lipid compositions: 1,2-dimyristoil-sn-glycero-3-phosphocholine (DMPC), 1,2-dimyristoylsn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and a binary mixture of DMPC/DMPG, in a wide range of peptide-to-lipid (P:L) molar ratios (0 to 1:7). DSC results indicate that, for both peptides, the interaction depends on membrane composition, with very different behavior for zwitterionic and anionic membranes. CD data show that, although the two peptides have different secondary structures in buffer (random coil for CA(1-7)M(2-9) and predominantly-sheet for CA(1-8)M(1-18)), they both adopt an R-helical structure in the presence of the membranes. Overall, results are compatible with a model involving a strong electrostatic surface interaction between the peptides and the negatively charged liposomes, which gives place to aggregation in the gel phase and precipitation after a threshold peptide concentration. In the case of zwitterionic membranes, a progressive surface coverage with peptide molecules destabilizes the membrane, eventually leading to membrane disruption. Moreover, delicate modulations in behavior were observed depending on the peptide.

Research paper thumbnail of Ruthenium-Based Anticancer Compounds: Insights into Their Cellular Targeting and Mechanism of Action

Research paper thumbnail of Half-Sandwich Ru(p-cymene) Compounds with Diphosphanes: In Vitro and In Vivo Evaluation As Potential Anticancer Metallodrugs

Research paper thumbnail of Unprecedented collateral sensitivity for cisplatin-resistant lung cancer cells presented by new ruthenium organometallic compounds

Inorganic Chemistry Frontiers

Ru compounds exhibit collateral sensitivity in cisplatin-resistant NSCLC and increase cisplatin a... more Ru compounds exhibit collateral sensitivity in cisplatin-resistant NSCLC and increase cisplatin activity by inhibiting efflux pumps.

Research paper thumbnail of Experimental Data on Novel Fe(Iii)-Complexes Containing Phenanthroline Derivatives for their Anticancer Properties

Research paper thumbnail of Interaction with Blood Proteins of a Ruthenium(II) Nitrofuryl Semicarbazone Complex: Effect on the Antitumoral Activity

Molecules

The steady rise in the cancer burden and grim statistics set a vital need for new therapeutic sol... more The steady rise in the cancer burden and grim statistics set a vital need for new therapeutic solutions. Given their high efficiency, metallodrugs are quite appealing in cancer chemotherapy. This work examined the anticancer activity of an anti-trypanosomal ruthenium-based compound bearing the 5-nitrofuryl pharmacophore, [RuII(dmso)2(5-nitro-2-furaldehyde semicarbazone)] (abbreviated as RuNTF; dmso is the dimethyl sulfoxide ligand). The cytotoxicity of RuNTF was evaluated in vitro against ovarian adenocarcinoma, hormone-dependent breast adenocarcinoma, prostate carcinoma (grade IV) and V79 lung fibroblasts human cells. The activity of RuNTF was similar to the benchmark metallodrug cisplatin for the breast line and inactive against the prostate line and lung fibroblasts. Given the known role of serum protein binding in drug bioavailability and the distribution via blood plasma, this study assessed the interaction of RuNTF with human serum albumin (HSA) by circular dichroism (CD) and ...