Damiano Cirri | Università degli Studi di Firenze (University of Florence) (original) (raw)
Papers by Damiano Cirri
Journal of Inorganic Biochemistry
Expert Opinion on Drug Discovery
Introduction: The COVID-19 pandemic poses an unprecedented challenge for the rapid discovery of d... more Introduction: The COVID-19 pandemic poses an unprecedented challenge for the rapid discovery of drugs against this life-threatening disease. Owing to the peculiar features of the metal centers that are currently used in medicinal chemistry, metallodrugs might offer an excellent opportunity to achieve this goal. Areas covered: Two main strategies for developing metal-based drugs against the SARS-CoV-2 are herein illustrated. Firstly, a few clinically approved metallodrugs could be evaluated in patients according to a 'drug repurposing' approach. To this respect, the gold drug auranofin seems a promising candidate, but some other clinically established metal compounds are worthy of a careful evaluation as well. On the other hand, libraries of inorganic compounds, featuring a large chemical diversity, should be screened to identify the most effective molecules. This second strategy might be assisted by a pathway-driven discovery approach arising from a preliminary knowledge of the mode of action, exploitable to inhibit the functional activities of the key viral proteins. Also, attention must be paid to selectivity and toxicity issues. Expert opinion: The medicinal inorganic chemistry community may offer a valuable contribution against COVID-19. The screening of metallodrugs' libraries can expand the explored 'chemical space' and increase the chance of finding effective anti-COVID agents.
Biomedicines
This article provides an overview of the various research approaches we have explored in recent y... more This article provides an overview of the various research approaches we have explored in recent years to improve metal-based agents for cancer or infection treatments. Although cisplatin, carboplatin, and oxaliplatin remain the cornerstones in tumor chemotherapy, the discovery and approval of novel inorganic anticancer drugs is a very slow process. Analogously, although a few promising inorganic drugs have found clinical application against parasitic or bacterial infections, their use remains relatively limited. Moreover, the discovery process is often affected by small therapeutic enhancements that are not attractive for the pharmaceutical industry. However, the availability of increasing mechanistic information for the modes of action of established inorganic drugs is fueling the exploration of various approaches for developing effective inorganic chemotherapy agents. Through a series of examples, some from our own research experience, we focus our attention on a number of promisi...
Molecules
Gold and silver N-heterocyclic carbenes (NHCs) are emerging for therapeutic applications. Multipl... more Gold and silver N-heterocyclic carbenes (NHCs) are emerging for therapeutic applications. Multiple techniques are here used to unveil the mechanistic details of the binding to different biosubstrates of bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) silver chloride [Ag(EIA)2]Cl and bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) gold chloride [Au(EIA)2]Cl. As the biosubstrates, we tested natural double-stranded DNA, synthetic RNA polynucleotides (single-poly(A), double-poly(A)poly(U) and triple-stranded poly(A)2poly(U)), DNA G-quadruplex structures (G4s), and bovine serum albumin (BSA) protein. Absorbance and fluorescence titrations, mass spectrometry together with melting and viscometry tests show significant differences in the binding features between silver and gold compounds. [Au(EIA)2]Cl covalently binds BSA. It is here evidenced that the selectivity is high: low affinity and external binding for all polynucleotides and G4s are found. Conversely, in the case of...
Dalton Transactions
AP-1 spontaneously aggregates in aqueous solutions. The structure of the adduct formed by an AP-1... more AP-1 spontaneously aggregates in aqueous solutions. The structure of the adduct formed by an AP-1 trimer with lysozyme offers insight into the process of the oligomer's growth.
Molecules
A group of triethylphosphine gold(I) and silver(I) complexes, structurally related to auranofin, ... more A group of triethylphosphine gold(I) and silver(I) complexes, structurally related to auranofin, were prepared and investigated as potential anticancer drug candidates. The antiproliferative properties of these metal compounds were assessed against two leukemia cell lines, i.e., CCRF-CEM and its multidrug-resistant counterpart, CEM/ADR5000. Interestingly, potent cytotoxic effects were disclosed for both series of compounds against leukemia cells, with IC50 values generally falling in the low-micromolar range, the gold derivatives being on the whole more effective than the silver analogues. Some initial structure-function relationships were drawn. Subsequently, the ability of the study compounds to inhibit the three main catalytic activities of the proteasome was investigated. Different patterns of enzyme inhibition emerged for the various metal complexes. Notably, gold compounds were able to inhibit effectively both the trypsin-like and chymotrypsin-like proteasome activities, being...
Journal of Inorganic Biochemistry
Journal of Inorganic Biochemistry
Hexane-bisammonium-type compounds containing lateral phthalimide moieties are well-established li... more Hexane-bisammonium-type compounds containing lateral phthalimide moieties are well-established ligands of the common allosteric binding site of muscarinic M(2) receptors. Previous structure-activity relationships (SAR) revealed two positively charged centers and two lateral phthalimide moieties in a defined arrangement to be essential of a high allosteric potency. The purpose of this study was to replace one carbonyl group of the phthalimides with hydrogens, hydroxy, alkoxy, phenyl, benzyl, and benzylidene groups in order to check the influence of these substituents on the allosteric activity in antagonist-linked receptors. The analysis of the quantitative SAR indicated that a high allosteric potency is related to a certain amount of rigidity as well as polarizibility and the ability to form hydrophobic interactions.
BioMetals
In the initial online publication, the given name of the first author was incorrectly displayed a... more In the initial online publication, the given name of the first author was incorrectly displayed and should have read Damiano. The original article has been corrected and the proper representation of the authors' names and their affiliation is also listed here. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
ACS Medicinal Chemistry Letters
Synthesis and characterization of Et 3 PAuI:………………………………………………… ……………………………………….2 LogP determinat... more Synthesis and characterization of Et 3 PAuI:………………………………………………… ……………………………………….2 LogP determination…………………………………………………..…………………………………………………………….………………2 Apoptosis plots………………………………………………………………………………………………………………………………….……3 Cell death and caspase activity…………………………………………………………………………………………………………………3 Cell growth inhibition studies (Sulforhodamine B assay)…………………………………………………………………………4 Tolerability studies………………………………………………………………………………………………………………………………….4 Biodistribution studies…………………………………………………………………………………………………………………………….4 In vivo anticancer activity evaluation xenograft subcutaneous models plots…………………………………………..7 NMR stability …………………………………………………………………………………………………………………………………………8
ChemMedChem
Supporting information for this article is given via a link at the end of the document.
Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, Jan 6, 2016
Three structurally related gold(I) carbene complexes with bulky hydrophobic ligands i.e. 1-3 were... more Three structurally related gold(I) carbene complexes with bulky hydrophobic ligands i.e. 1-3 were investigated in solution for further consideration as candidate anticancer agents. Cytotoxic assays were subsequently conducted on bone marrow-derived preosteoclast cell line of human origin (FLG 29.1) and human colon cancer cells (HCT-116). A far greater cytotoxic activity was measured for compound 1 against HCT-116 cells compared to 2 and 3; conversely, all compounds were highly and similarly active against FLG 29.1 cells. Results obtained for the reaction of complexes 1 and 2 with RNase A documented the occurrence of a weak interaction with this model protein and the formation of a tiny amount of the corresponding adduct. Moreover, a certain reactivity of the complex 2 was also detected toward GSH. The general implications of the obtained results are discussed.
Journal of Inorganic Biochemistry
Expert Opinion on Drug Discovery
Introduction: The COVID-19 pandemic poses an unprecedented challenge for the rapid discovery of d... more Introduction: The COVID-19 pandemic poses an unprecedented challenge for the rapid discovery of drugs against this life-threatening disease. Owing to the peculiar features of the metal centers that are currently used in medicinal chemistry, metallodrugs might offer an excellent opportunity to achieve this goal. Areas covered: Two main strategies for developing metal-based drugs against the SARS-CoV-2 are herein illustrated. Firstly, a few clinically approved metallodrugs could be evaluated in patients according to a 'drug repurposing' approach. To this respect, the gold drug auranofin seems a promising candidate, but some other clinically established metal compounds are worthy of a careful evaluation as well. On the other hand, libraries of inorganic compounds, featuring a large chemical diversity, should be screened to identify the most effective molecules. This second strategy might be assisted by a pathway-driven discovery approach arising from a preliminary knowledge of the mode of action, exploitable to inhibit the functional activities of the key viral proteins. Also, attention must be paid to selectivity and toxicity issues. Expert opinion: The medicinal inorganic chemistry community may offer a valuable contribution against COVID-19. The screening of metallodrugs' libraries can expand the explored 'chemical space' and increase the chance of finding effective anti-COVID agents.
Biomedicines
This article provides an overview of the various research approaches we have explored in recent y... more This article provides an overview of the various research approaches we have explored in recent years to improve metal-based agents for cancer or infection treatments. Although cisplatin, carboplatin, and oxaliplatin remain the cornerstones in tumor chemotherapy, the discovery and approval of novel inorganic anticancer drugs is a very slow process. Analogously, although a few promising inorganic drugs have found clinical application against parasitic or bacterial infections, their use remains relatively limited. Moreover, the discovery process is often affected by small therapeutic enhancements that are not attractive for the pharmaceutical industry. However, the availability of increasing mechanistic information for the modes of action of established inorganic drugs is fueling the exploration of various approaches for developing effective inorganic chemotherapy agents. Through a series of examples, some from our own research experience, we focus our attention on a number of promisi...
Molecules
Gold and silver N-heterocyclic carbenes (NHCs) are emerging for therapeutic applications. Multipl... more Gold and silver N-heterocyclic carbenes (NHCs) are emerging for therapeutic applications. Multiple techniques are here used to unveil the mechanistic details of the binding to different biosubstrates of bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) silver chloride [Ag(EIA)2]Cl and bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) gold chloride [Au(EIA)2]Cl. As the biosubstrates, we tested natural double-stranded DNA, synthetic RNA polynucleotides (single-poly(A), double-poly(A)poly(U) and triple-stranded poly(A)2poly(U)), DNA G-quadruplex structures (G4s), and bovine serum albumin (BSA) protein. Absorbance and fluorescence titrations, mass spectrometry together with melting and viscometry tests show significant differences in the binding features between silver and gold compounds. [Au(EIA)2]Cl covalently binds BSA. It is here evidenced that the selectivity is high: low affinity and external binding for all polynucleotides and G4s are found. Conversely, in the case of...
Dalton Transactions
AP-1 spontaneously aggregates in aqueous solutions. The structure of the adduct formed by an AP-1... more AP-1 spontaneously aggregates in aqueous solutions. The structure of the adduct formed by an AP-1 trimer with lysozyme offers insight into the process of the oligomer's growth.
Molecules
A group of triethylphosphine gold(I) and silver(I) complexes, structurally related to auranofin, ... more A group of triethylphosphine gold(I) and silver(I) complexes, structurally related to auranofin, were prepared and investigated as potential anticancer drug candidates. The antiproliferative properties of these metal compounds were assessed against two leukemia cell lines, i.e., CCRF-CEM and its multidrug-resistant counterpart, CEM/ADR5000. Interestingly, potent cytotoxic effects were disclosed for both series of compounds against leukemia cells, with IC50 values generally falling in the low-micromolar range, the gold derivatives being on the whole more effective than the silver analogues. Some initial structure-function relationships were drawn. Subsequently, the ability of the study compounds to inhibit the three main catalytic activities of the proteasome was investigated. Different patterns of enzyme inhibition emerged for the various metal complexes. Notably, gold compounds were able to inhibit effectively both the trypsin-like and chymotrypsin-like proteasome activities, being...
Journal of Inorganic Biochemistry
Journal of Inorganic Biochemistry
Hexane-bisammonium-type compounds containing lateral phthalimide moieties are well-established li... more Hexane-bisammonium-type compounds containing lateral phthalimide moieties are well-established ligands of the common allosteric binding site of muscarinic M(2) receptors. Previous structure-activity relationships (SAR) revealed two positively charged centers and two lateral phthalimide moieties in a defined arrangement to be essential of a high allosteric potency. The purpose of this study was to replace one carbonyl group of the phthalimides with hydrogens, hydroxy, alkoxy, phenyl, benzyl, and benzylidene groups in order to check the influence of these substituents on the allosteric activity in antagonist-linked receptors. The analysis of the quantitative SAR indicated that a high allosteric potency is related to a certain amount of rigidity as well as polarizibility and the ability to form hydrophobic interactions.
BioMetals
In the initial online publication, the given name of the first author was incorrectly displayed a... more In the initial online publication, the given name of the first author was incorrectly displayed and should have read Damiano. The original article has been corrected and the proper representation of the authors' names and their affiliation is also listed here. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
ACS Medicinal Chemistry Letters
Synthesis and characterization of Et 3 PAuI:………………………………………………… ……………………………………….2 LogP determinat... more Synthesis and characterization of Et 3 PAuI:………………………………………………… ……………………………………….2 LogP determination…………………………………………………..…………………………………………………………….………………2 Apoptosis plots………………………………………………………………………………………………………………………………….……3 Cell death and caspase activity…………………………………………………………………………………………………………………3 Cell growth inhibition studies (Sulforhodamine B assay)…………………………………………………………………………4 Tolerability studies………………………………………………………………………………………………………………………………….4 Biodistribution studies…………………………………………………………………………………………………………………………….4 In vivo anticancer activity evaluation xenograft subcutaneous models plots…………………………………………..7 NMR stability …………………………………………………………………………………………………………………………………………8
ChemMedChem
Supporting information for this article is given via a link at the end of the document.
Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, Jan 6, 2016
Three structurally related gold(I) carbene complexes with bulky hydrophobic ligands i.e. 1-3 were... more Three structurally related gold(I) carbene complexes with bulky hydrophobic ligands i.e. 1-3 were investigated in solution for further consideration as candidate anticancer agents. Cytotoxic assays were subsequently conducted on bone marrow-derived preosteoclast cell line of human origin (FLG 29.1) and human colon cancer cells (HCT-116). A far greater cytotoxic activity was measured for compound 1 against HCT-116 cells compared to 2 and 3; conversely, all compounds were highly and similarly active against FLG 29.1 cells. Results obtained for the reaction of complexes 1 and 2 with RNase A documented the occurrence of a weak interaction with this model protein and the formation of a tiny amount of the corresponding adduct. Moreover, a certain reactivity of the complex 2 was also detected toward GSH. The general implications of the obtained results are discussed.