Laura Baldomà | University of Barcelona (original) (raw)
Papers by Laura Baldomà
Colloids and Surfaces B: Biointerfaces, Nov 30, 2023
SE HA PURIFICADO EL ENZIMA LACTALDEHIDO DESHIDROGENASA DE E.COLI EL CUAL PRESENTA UNA ESTRUCTURA ... more SE HA PURIFICADO EL ENZIMA LACTALDEHIDO DESHIDROGENASA DE E.COLI EL CUAL PRESENTA UNA ESTRUCTURA TETRAMERICA FORMADA POR CUATRO SUBUNIDADES DE 55.000 DALTONS Y 4 CENTROS DE UNION AL NAD. CATALIZA UNA REACCION IRREVERSIBLE MOSTRANDO UN PH OPTIMO DE 9 5. ES ACTIVO SOBRE GAMMA-HIDROXI- (LACTALDEHIDO GLICERALDEHIDO GLICOLALDEHIDO) Y GAMMA-CETO-ALDEHIDOS (METILGLIOXAL). EL CALCULO DE LA EFICIENCIA CATALITICA DEL ENZIMA (VMAX/KM) INDICA QUE EL LACTALDEHIDO SERIA EL SUSTRATO FISIOLOGICO. LOS ESTUDIOS GENETICOS ESTRUCTURALES E INMUNOLOGICOS DEL ENZIMA SINTETIZADO POR VARIAS CEPAS DE E.COLI DEMUESTRAN LA EXISTENCIA DE UNA UNICA FORMA ENZIMATICA LA CUAL ES UTILIZADA CONJUNTAMENTE POR LOS METABOLISMOS DE L-FUCOSA L-RAMNOSA L-PROPANODIOL (CUYO INDUCTOR ES EL LACTALDEHIDO) ETILENGLICOL (EL CUAL INDUCE VIA GLICOLALDEHIDO) Y GLUTAMATO (SE DESCONOCE CUAL ES EL INTERMEDIARIO QUE ACTUA COMO INDUCTOR). EL ANALISIS DE MUTANTES HA EVIDENCIADO LA EXISTENCIA DE UN SOLO GEN REGULADOR SITUADO CERCA DEL LOCUS FUC Y UN SOLO GEN ESTRUCTURAL ASI COMO UN CONTROL DE TIPO POSITIVO PARA SU EXPRESION GENICA.
ACS Applied Nano Materials
The low bioavailability of curcuminoids (CCMoids) limits their use in the treatment of inflammato... more The low bioavailability of curcuminoids (CCMoids) limits their use in the treatment of inflammatory skin diseases. Our work shows that this constraint can be overcome upon their incorporation into supramolecular hydrogels assembled from a gemini-imidazolium amphiphilic gelator. Three structural CCMoid analogues were used to prepare supramolecular hydrogels, and it was observed that the concentration of both the gelator and CCMoid and the proportion of solvents influence the selfassembly process. Moreover, the mechanical properties of the nanostructured gels were studied to find the optimum gels, which were then further characterized microscopically, and their ability to release the CCMoid was evaluated. The physicochemical properties of the CCMoids play a fundamental role in the interaction with the gelator, influencing not only the gelation but also the morphology at the microscopic level, the mechanical properties, and the biopharmaceutical behavior such as the amount of CCMoid released from the gels. The nanostructured supramolecular hydrogels, which contain the CCMoids at much lower concentrations (μg/mL) in comparison to other products, promote the penetration of the CCMoids within the skin, but not their transdermal permeation, thus preventing any possible systemic effects and representing a safer option for topical administration. As a result, the CCMoid-containing hydrogels can effectively reduce skin inflammation in vivo, proving that these supramolecular systems are excellent alternatives in the treatment of inflammatory skin diseases.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Bacterial populations in mouse stool, and ileal and colonic mucus at five days postinoculation wi... more Bacterial populations in mouse stool, and ileal and colonic mucus at five days postinoculation with the indicated strains. Table S2. Variations in Sat sequence among E.coli strains. (PDF 165 kb)
Expression analysis of the transcriptional fusion sat-gfp mut3.1 in EcN grown in diferent conditi... more Expression analysis of the transcriptional fusion sat-gfp mut3.1 in EcN grown in diferent conditions. (PDF 173 kb)
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
The UlaG protein family defines novel structural and functional motifs grafted on an ancient
Nutrients, May 24, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Nutrients
Microbiota–host communication is primarily achieved by secreted factors that can penetrate the mu... more Microbiota–host communication is primarily achieved by secreted factors that can penetrate the mucosal surface, such as extracellular membrane vesicles (EVs). The EVs released by the gut microbiota have been extensively studied in cellular and experimental models of human diseases. However, little is known about their in vivo effects in early life, specifically regarding immune and intestinal maturation. This study aimed to investigate the effects of daily administration of EVs from probiotic and commensal E. coli strains in healthy suckling rats during the first 16 days of life. On days 8 and 16, we assessed various intestinal and systemic variables in relation to animal growth, humoral and cellular immunity, epithelial barrier maturation, and intestinal architecture. On day 16, animals given probiotic/microbiota EVs exhibited higher levels of plasma IgG, IgA, and IgM and a greater proportion of Tc, NK, and NKT cells in the spleen. In the small intestine, EVs increased the villi ar...
Proteómica: revista de la Sociedad Española de Proteómica, 2009
Journal of Bacteriology, Mar 15, 2004
The ula regulon, responsible for the utilization of L-ascorbate in Escherichia coli, is formed by... more The ula regulon, responsible for the utilization of L-ascorbate in Escherichia coli, is formed by two divergently transcribed operons, ulaG and ulaABCDEF. The regulon is negatively regulated by a repressor of the DeoR family which is encoded by the constitutive gene ulaR located downstream of ulaG. Full repression of the ula regulon requires simultaneous interaction of the repressor with both divergent promoters and seems to be dependent on repressor-mediated DNA loop formation, which is helped by the action of integration host factor. Two operator sites have been identified in each promoter. Lack of either of the two sets of operators partially relieved the repression of the other operon; thus, each promoter is dependent on the UlaR operator sites of the other promoter to enhance repression. Electrophoretic mobility shift assays with purified UlaR protein and promoter deletion analyses revealed a conserved sequence, present in each of the four operators, acting as a UlaR binding site. Glucose represses the ula regulon via at least two mechanisms, one dependent on cyclic AMP (cAMP)-cAMP receptor protein (CRP) and the other (possibly inducer exclusion) independent of it. Glucose effects mediated by other global regulators cannot be ruled out with the present information. Changes in cAMP-CRP levels affected only the expression of the ulaABCDEF operon.
Journal of Bacteriology, May 1, 1988
When grown anaerobically on L-rhamnose, Salmonella typhimurium excreted 1,2-propanediol as a ferm... more When grown anaerobically on L-rhamnose, Salmonella typhimurium excreted 1,2-propanediol as a fermentation product. Upon exhaustion of the methyl pentose, 1,2-propanediol was recaptured and further metabolized, provided the culture was kept under anaerobic conditions. n-Propanol and propionate were found in the medium as end products of this process at concentrations one-half that of 1,2-propanediol. As in Klebsiella pneumoniae (T. Toraya, S. Honda, and S. Fukui, J. Bacteriol. 139:3947, 1979), a diol dehydratase which transforms 1,2-propanediol to propionaldehyde and the enzymes involved in a dismutation that converts propionaldehyde to n-propanol and propionate were induced in S. typhimurium cultures able to transform 1,2-propanediol anaerobically.
Dalton Transactions, 2018
The synthesis of three new cyclometallated platinum(II) compounds containing a para-tolyl ligand ... more The synthesis of three new cyclometallated platinum(II) compounds containing a para-tolyl ligand and a tridentate [C,N,N'] (cm1) or a bidentate [C,N] ligand and an additional ligand such as SEt2 (cm2) or Ph3 (cm3) is reported. The X-ray molecular structure of platinum(II) compound cm3 is also presented. Intermolecular oxidative addition of methyl iodide or iodine upon cm1, cm2 and cm3 produced six novel cyclometallated platinum(IV) compounds. The cytotoxic activity against a panel of human adenocarcinoma cell lines (A-549 lung, MDA-MB-231 and MCF-7 breast, and HCT-116 colon), DNA interaction, topoisomerase I, IIα, and cathepsin B inhibition, and cell cycle arrest, apoptosis and ROS generation of the investigated complexes are presented. The best results for antiproliferative activity were obtained for platinum (IV) compounds cm1MeI and cm1I2 arising from oxidative addition of methyl iodide and iodine, respectively, to cm1. Cyclometallated platinum(IV) compounds cm1MeI and cm3MeI induce significant changes in the mobility of DNA and, in addition, cm1MeI, cm3MeI and cm1I2, showed considerable topoisomerase IIα inhibitory activity. Moreover, the compounds exhibiting the higher antiproliferative activity (cm1MeI and cm1I2) were found to generate ROS and to supress HCT-116 colon cancer cell growth by a mixture of cell cycle arrest and apoptosis induction. 1H NMR experiments carried out in a buffered aqueous medium (pH 7.40) indicate that compound cm1MeI is not reduced by common biologically relevant reducing agents such as ascorbic acid, glutathione or cysteine.
Journal of Bacteriology, Nov 1, 2002
Mutations in yjfQ allowed us to identify this gene as the regulator of the operon yjfS-X (ula ope... more Mutations in yjfQ allowed us to identify this gene as the regulator of the operon yjfS-X (ula operon), reported to be involved in L-ascorbate metabolism. Inactivation of this gene renders constitutive the expression of the ula operon, indicating that YjfQ acts as a repressor. We also demonstrate that this repressor regulates the nearby yjfR gene, which in this way constitutes a regulon with the ula operon.
Dalton Transactions, 2017
The synthesis of six novel cyclometallated platinum(IV) iodido complexes is accomplished by inter... more The synthesis of six novel cyclometallated platinum(IV) iodido complexes is accomplished by intermolecular oxidative addition of methyl iodide (compounds 2a-2c) or iodine (compounds 3a-3c) upon cyclometallated platinum(II) compounds [PtX{(CH3)2N(CH2)3NCH(4-ClC6H3)}] (1a-1c: X = Cl, CH3 or I). The X-ray molecular structures of platinum(II) compound 1c and platinum(IV) compounds 3b and 3a' (an isomer of 3a) are reported. The cytotoxic activity against a panel of human adenocarcinoma cell lines (A-549 lung, MDA-MB-231 and MCF-7 breast, and HCT-116 colon), DNA interaction, topoisomerase I, IIα, and cathepsin B inhibition, and cell cycle arrest, apoptosis and ROS generation of the investigated complexes are presented. Remarkable antiproliferative activity was observed for most of the synthesized cycloplatinated compounds (series 1-3) in all the selected carcinoma cell lines. The best inhibition was provided for the octahedral platinum(IV) compounds 2a-2c exhibiting a methyl and an iodido axial ligand. Preliminary biological results point to a different mechanism of action for the investigated compounds. Cyclometallated platinum(II) compounds 1a-1c modify the DNA migration as cisplatin. In contrast, cyclometallated platinum(IV) compounds 2a-2c and 3a-3c did not modify the DNA tertiary structure neither in the absence nor in the presence of ascorbic acid, which made them incapable of reducing platinum(IV) compounds 2b and 2c in a buffered aqueous medium (pH 7.40) according to 1H NMR experiments. Remarkable topoisomerase IIα inhibitory activity is reported for platinum(IV) complexes 2b and 3a and in addition, for the last one, a moderate cathepsin B inhibition is reported. Cell cycle arrest (decrease in G0/G1 and G2 phases and arrest in the S phase), induction of apoptosis and ROS generation are related to the antiproliferative activity of some representative octahedral cyclometallated platinum(IV) compounds (2band 2c).
European journal of biochemistry, Sep 1, 1994
ABSTRACT
Colloids and Surfaces B: Biointerfaces, Nov 30, 2023
SE HA PURIFICADO EL ENZIMA LACTALDEHIDO DESHIDROGENASA DE E.COLI EL CUAL PRESENTA UNA ESTRUCTURA ... more SE HA PURIFICADO EL ENZIMA LACTALDEHIDO DESHIDROGENASA DE E.COLI EL CUAL PRESENTA UNA ESTRUCTURA TETRAMERICA FORMADA POR CUATRO SUBUNIDADES DE 55.000 DALTONS Y 4 CENTROS DE UNION AL NAD. CATALIZA UNA REACCION IRREVERSIBLE MOSTRANDO UN PH OPTIMO DE 9 5. ES ACTIVO SOBRE GAMMA-HIDROXI- (LACTALDEHIDO GLICERALDEHIDO GLICOLALDEHIDO) Y GAMMA-CETO-ALDEHIDOS (METILGLIOXAL). EL CALCULO DE LA EFICIENCIA CATALITICA DEL ENZIMA (VMAX/KM) INDICA QUE EL LACTALDEHIDO SERIA EL SUSTRATO FISIOLOGICO. LOS ESTUDIOS GENETICOS ESTRUCTURALES E INMUNOLOGICOS DEL ENZIMA SINTETIZADO POR VARIAS CEPAS DE E.COLI DEMUESTRAN LA EXISTENCIA DE UNA UNICA FORMA ENZIMATICA LA CUAL ES UTILIZADA CONJUNTAMENTE POR LOS METABOLISMOS DE L-FUCOSA L-RAMNOSA L-PROPANODIOL (CUYO INDUCTOR ES EL LACTALDEHIDO) ETILENGLICOL (EL CUAL INDUCE VIA GLICOLALDEHIDO) Y GLUTAMATO (SE DESCONOCE CUAL ES EL INTERMEDIARIO QUE ACTUA COMO INDUCTOR). EL ANALISIS DE MUTANTES HA EVIDENCIADO LA EXISTENCIA DE UN SOLO GEN REGULADOR SITUADO CERCA DEL LOCUS FUC Y UN SOLO GEN ESTRUCTURAL ASI COMO UN CONTROL DE TIPO POSITIVO PARA SU EXPRESION GENICA.
ACS Applied Nano Materials
The low bioavailability of curcuminoids (CCMoids) limits their use in the treatment of inflammato... more The low bioavailability of curcuminoids (CCMoids) limits their use in the treatment of inflammatory skin diseases. Our work shows that this constraint can be overcome upon their incorporation into supramolecular hydrogels assembled from a gemini-imidazolium amphiphilic gelator. Three structural CCMoid analogues were used to prepare supramolecular hydrogels, and it was observed that the concentration of both the gelator and CCMoid and the proportion of solvents influence the selfassembly process. Moreover, the mechanical properties of the nanostructured gels were studied to find the optimum gels, which were then further characterized microscopically, and their ability to release the CCMoid was evaluated. The physicochemical properties of the CCMoids play a fundamental role in the interaction with the gelator, influencing not only the gelation but also the morphology at the microscopic level, the mechanical properties, and the biopharmaceutical behavior such as the amount of CCMoid released from the gels. The nanostructured supramolecular hydrogels, which contain the CCMoids at much lower concentrations (μg/mL) in comparison to other products, promote the penetration of the CCMoids within the skin, but not their transdermal permeation, thus preventing any possible systemic effects and representing a safer option for topical administration. As a result, the CCMoid-containing hydrogels can effectively reduce skin inflammation in vivo, proving that these supramolecular systems are excellent alternatives in the treatment of inflammatory skin diseases.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Bacterial populations in mouse stool, and ileal and colonic mucus at five days postinoculation wi... more Bacterial populations in mouse stool, and ileal and colonic mucus at five days postinoculation with the indicated strains. Table S2. Variations in Sat sequence among E.coli strains. (PDF 165 kb)
Expression analysis of the transcriptional fusion sat-gfp mut3.1 in EcN grown in diferent conditi... more Expression analysis of the transcriptional fusion sat-gfp mut3.1 in EcN grown in diferent conditions. (PDF 173 kb)
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
The UlaG protein family defines novel structural and functional motifs grafted on an ancient
Nutrients, May 24, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Nutrients
Microbiota–host communication is primarily achieved by secreted factors that can penetrate the mu... more Microbiota–host communication is primarily achieved by secreted factors that can penetrate the mucosal surface, such as extracellular membrane vesicles (EVs). The EVs released by the gut microbiota have been extensively studied in cellular and experimental models of human diseases. However, little is known about their in vivo effects in early life, specifically regarding immune and intestinal maturation. This study aimed to investigate the effects of daily administration of EVs from probiotic and commensal E. coli strains in healthy suckling rats during the first 16 days of life. On days 8 and 16, we assessed various intestinal and systemic variables in relation to animal growth, humoral and cellular immunity, epithelial barrier maturation, and intestinal architecture. On day 16, animals given probiotic/microbiota EVs exhibited higher levels of plasma IgG, IgA, and IgM and a greater proportion of Tc, NK, and NKT cells in the spleen. In the small intestine, EVs increased the villi ar...
Proteómica: revista de la Sociedad Española de Proteómica, 2009
Journal of Bacteriology, Mar 15, 2004
The ula regulon, responsible for the utilization of L-ascorbate in Escherichia coli, is formed by... more The ula regulon, responsible for the utilization of L-ascorbate in Escherichia coli, is formed by two divergently transcribed operons, ulaG and ulaABCDEF. The regulon is negatively regulated by a repressor of the DeoR family which is encoded by the constitutive gene ulaR located downstream of ulaG. Full repression of the ula regulon requires simultaneous interaction of the repressor with both divergent promoters and seems to be dependent on repressor-mediated DNA loop formation, which is helped by the action of integration host factor. Two operator sites have been identified in each promoter. Lack of either of the two sets of operators partially relieved the repression of the other operon; thus, each promoter is dependent on the UlaR operator sites of the other promoter to enhance repression. Electrophoretic mobility shift assays with purified UlaR protein and promoter deletion analyses revealed a conserved sequence, present in each of the four operators, acting as a UlaR binding site. Glucose represses the ula regulon via at least two mechanisms, one dependent on cyclic AMP (cAMP)-cAMP receptor protein (CRP) and the other (possibly inducer exclusion) independent of it. Glucose effects mediated by other global regulators cannot be ruled out with the present information. Changes in cAMP-CRP levels affected only the expression of the ulaABCDEF operon.
Journal of Bacteriology, May 1, 1988
When grown anaerobically on L-rhamnose, Salmonella typhimurium excreted 1,2-propanediol as a ferm... more When grown anaerobically on L-rhamnose, Salmonella typhimurium excreted 1,2-propanediol as a fermentation product. Upon exhaustion of the methyl pentose, 1,2-propanediol was recaptured and further metabolized, provided the culture was kept under anaerobic conditions. n-Propanol and propionate were found in the medium as end products of this process at concentrations one-half that of 1,2-propanediol. As in Klebsiella pneumoniae (T. Toraya, S. Honda, and S. Fukui, J. Bacteriol. 139:3947, 1979), a diol dehydratase which transforms 1,2-propanediol to propionaldehyde and the enzymes involved in a dismutation that converts propionaldehyde to n-propanol and propionate were induced in S. typhimurium cultures able to transform 1,2-propanediol anaerobically.
Dalton Transactions, 2018
The synthesis of three new cyclometallated platinum(II) compounds containing a para-tolyl ligand ... more The synthesis of three new cyclometallated platinum(II) compounds containing a para-tolyl ligand and a tridentate [C,N,N'] (cm1) or a bidentate [C,N] ligand and an additional ligand such as SEt2 (cm2) or Ph3 (cm3) is reported. The X-ray molecular structure of platinum(II) compound cm3 is also presented. Intermolecular oxidative addition of methyl iodide or iodine upon cm1, cm2 and cm3 produced six novel cyclometallated platinum(IV) compounds. The cytotoxic activity against a panel of human adenocarcinoma cell lines (A-549 lung, MDA-MB-231 and MCF-7 breast, and HCT-116 colon), DNA interaction, topoisomerase I, IIα, and cathepsin B inhibition, and cell cycle arrest, apoptosis and ROS generation of the investigated complexes are presented. The best results for antiproliferative activity were obtained for platinum (IV) compounds cm1MeI and cm1I2 arising from oxidative addition of methyl iodide and iodine, respectively, to cm1. Cyclometallated platinum(IV) compounds cm1MeI and cm3MeI induce significant changes in the mobility of DNA and, in addition, cm1MeI, cm3MeI and cm1I2, showed considerable topoisomerase IIα inhibitory activity. Moreover, the compounds exhibiting the higher antiproliferative activity (cm1MeI and cm1I2) were found to generate ROS and to supress HCT-116 colon cancer cell growth by a mixture of cell cycle arrest and apoptosis induction. 1H NMR experiments carried out in a buffered aqueous medium (pH 7.40) indicate that compound cm1MeI is not reduced by common biologically relevant reducing agents such as ascorbic acid, glutathione or cysteine.
Journal of Bacteriology, Nov 1, 2002
Mutations in yjfQ allowed us to identify this gene as the regulator of the operon yjfS-X (ula ope... more Mutations in yjfQ allowed us to identify this gene as the regulator of the operon yjfS-X (ula operon), reported to be involved in L-ascorbate metabolism. Inactivation of this gene renders constitutive the expression of the ula operon, indicating that YjfQ acts as a repressor. We also demonstrate that this repressor regulates the nearby yjfR gene, which in this way constitutes a regulon with the ula operon.
Dalton Transactions, 2017
The synthesis of six novel cyclometallated platinum(IV) iodido complexes is accomplished by inter... more The synthesis of six novel cyclometallated platinum(IV) iodido complexes is accomplished by intermolecular oxidative addition of methyl iodide (compounds 2a-2c) or iodine (compounds 3a-3c) upon cyclometallated platinum(II) compounds [PtX{(CH3)2N(CH2)3NCH(4-ClC6H3)}] (1a-1c: X = Cl, CH3 or I). The X-ray molecular structures of platinum(II) compound 1c and platinum(IV) compounds 3b and 3a' (an isomer of 3a) are reported. The cytotoxic activity against a panel of human adenocarcinoma cell lines (A-549 lung, MDA-MB-231 and MCF-7 breast, and HCT-116 colon), DNA interaction, topoisomerase I, IIα, and cathepsin B inhibition, and cell cycle arrest, apoptosis and ROS generation of the investigated complexes are presented. Remarkable antiproliferative activity was observed for most of the synthesized cycloplatinated compounds (series 1-3) in all the selected carcinoma cell lines. The best inhibition was provided for the octahedral platinum(IV) compounds 2a-2c exhibiting a methyl and an iodido axial ligand. Preliminary biological results point to a different mechanism of action for the investigated compounds. Cyclometallated platinum(II) compounds 1a-1c modify the DNA migration as cisplatin. In contrast, cyclometallated platinum(IV) compounds 2a-2c and 3a-3c did not modify the DNA tertiary structure neither in the absence nor in the presence of ascorbic acid, which made them incapable of reducing platinum(IV) compounds 2b and 2c in a buffered aqueous medium (pH 7.40) according to 1H NMR experiments. Remarkable topoisomerase IIα inhibitory activity is reported for platinum(IV) complexes 2b and 3a and in addition, for the last one, a moderate cathepsin B inhibition is reported. Cell cycle arrest (decrease in G0/G1 and G2 phases and arrest in the S phase), induction of apoptosis and ROS generation are related to the antiproliferative activity of some representative octahedral cyclometallated platinum(IV) compounds (2band 2c).
European journal of biochemistry, Sep 1, 1994
ABSTRACT