1,721,103 research outputs found
Considerazioni sulla rilettura di CIE5992
No full textDal riesame congiunto di carattere archeologico, epigrafico, linguistico dell'iscrizione ceretana del periodo orientalizzante recente rinvenuta sotto il tumulo delle Ginestre, emergono spunti per lo studio delle pratiche funerarie etrusche in rapporto a aspetti finora poco esplorati della cosmologia e della religione degli Etruschi
Artificial metalloenzymes based on vancomycin for stereoselective catalysis in aqueous media
Full text linkBackground: Artificial metalloenzymes, stemming from the combination of transition metal catalysts embedded within a biological environment, have recently risen up as a promising approach to merge the reactivity of metal-based catalysis and the specificity of biocatalysis. Dalbapeptides, such as vancomycin, teicoplanin and ristocetin are variously substituted heptapeptides whose antibiotic activity depends on their binding to the D-Ala-D-Ala dimer of peptidoglycan precursors thus resulting in the inhibition of cell wall biosynthesis. In this system, indeed, the source of chirality is due to the presence not only of the aminoacidic chain, but also from the atropoisomerism of their structure. This interaction is stabilized by an array of hydrophobic interactions and five key hydrogen bonds and it is marked by such a low dissociation constant (KD = ~10-17 M).
Objective: starting from this background, dalbapeptides can be employed as an innovative alternative to the classical biotin/(strept)avidin second sphere coordination system.
Methods: In this context, aminoethylbenzensulfonamide ligands decorated with the D-Ala-D-Ala dimer at different positions of the phenyl ring were employed for the synthesis of the hybrid catalysts in association with an iridium centre. In the presence of vancomycin, a new class of artificial reductases was obtained and applied to the stereoselective synthesis of chiral cyclic in different aqueous media.
Results: An encouraging 48% (S) e.e. was obtained in the asymmetric reduction of the salsolidine precursor in NaOAc 0.1 M buffer at pH 5 whereas in the case of the most demanding isoquinoline substrates, the meta-artificial metalloenzyme afforded the product in an outstanding 71% (S) e.e. when applied to quinaldine.
Conclusion: The Van/ D-Ala-D-Ala dimer system resulted particularly sensitive to pH variations, thus indicating an interesting change in the conformational arrangement of Van. Indeed, the system shows remarkable potential for the synthesis of chiral sultam precursors under green reaction conditions
New platinum-based chemotherapeutics: a journey beyond cisplatin
Full text linkThe discovery of cisplatin and its later approved derivatives started a new era in the bioinorganic medicinal chemistry field but the persistence of severe side-effects along with the emerging of drug resistance evoke the need of a new generation of transition metal-based chemotherapeutics. The starting point of this journey was the preparation of diamine ligands derived from variously substituted N-methyl-2-aminomethyl imidazoles.1 By introducing differently-long saturated and unsaturated chains at N1, the lipophilicity and the consequent cytotoxicity of the corresponding Pt(II)-complexes was modulated whereas its substitution with the 1,2,5-oxadiazole moiety selectively introduced the ability to simultaneously interact with DNA and to interrupt STAT3 signalling pathway.2 Breaking the assumption that bifunctionality is necessary for antiproliferative activity, a series of monofunctional cationic platinum complexes were synthesised showing a potent cytotoxic effect toward triple-negative breast cancer cells and in cancer cell lines partially resistant to cisplatin. Moreover, the prominent stability of this class of platinum complexes suggested also a possible application for MSCs loading to use for advanced cell therapy.3 Moving forward in this field, the effect of the bidentate ligands on the biological activity was highlighted showing for the Pt-8-aminoquinoline series a different biological profile.4 In order to gain some mechanistic insights, the interaction of such platinum-based compounds with some model proteins was investigated through ESI-MS analysis.
Since an increasing interest has recently arisen in the development of platinum based theranostic agents, indeed, a series of cyclometalated anionic Pt(II) complexes carrying tetrabromocatechol or alizarine as O^O chelating ligands was developed. This last series of platinum complexes displayed enhanced cytotoxicity toward triple-negative breast cancer (TNBC) and they furthermore resulted emissive in solution.5 Moreover, fluorescence confocal analysis showed their localization in the perinuclear region of MDA-MB231 cells proving their ability to serve as luminescent theranostic probes
New artificial imine reductases based on an iridium/ vancomycin system for the asymmetric reduction of cyclic imines
No full textArtificial metalloenzymes, deriving from transition metal catalysts embedding within a biological environment, have recently risen up as a promising synthetic tool able to combine the reactivity of metal-based catalysis with the specificity of biocatalysis.1 Dalbapeptides, such as vancomycin, teicoplanin and ristocetin are variously substituted heptapeptides whose antibiotic activity relies on their binding to the D-Ala-D-Ala dimer of peptidoglycan precursors thus leading to an irreversible inhibition of cell wall biosynthesis. This interaction is marked by such a low dissociation constant (KD =~10-17M) that it makes vancomycin-based systems an innovative alternative to the classical biotin/(strept)avidin technology.2,3
In this context, a class of aminoethylbenzensulfonamide ligands functionalized with the D-Ala-D-Ala dimer were employed for the synthesis of hybrid catalysts in association with an iridium centre. In the presence of vancomycin, a new class of artificial reductases was obtained and applied to the Asymmetric Transfer Hydrogenation (ATH) of model imine substrates in different aqueous media. An encouraging 48% (S) e.e. was obtained in the asymmetric reduction of the salsolidine precursor in CH3COONa 0.1 M buffer at pH 5 whereas in the case of quinolines, the meta-artificial metalloenzyme afforded the product in a significant 70% (S) e.e. when applied to quinaldine. Moreover, an unprecedented 35% (R) e.e. in the enantioselective reduction of chiral sultam precursor 3-methylbenzo[d]isothiazole-1,1-dioxide was realized under green reaction conditions
In vitro anticancer activity evaluation of new cationic platinum(II) complexes based on imidazole mojety
No full textPlatinum based-drugs currently used in therapy, i.e. cisplatin and its second and third generation derivatives carboplatin and oxaliplatin, were established to elicit their cytotoxic effect through the formation of bifunctional intra- and interstrand DNA adducts at the guanosine residues.
Since the discovery of the potent antiproliferative activity of the platinum triamine complex phenanthriplatin and of its analogues, the mechanism of action of monofunctional platinum compounds as anticancer agents have been deeply investigated.1,2
This class of platinum complexes bearing only one labile ligand is able to form only a single covalent bond at the N7 position of guanine residues without significantly bending or unwinding the double helix but indeed forming lesions of such a shape that result able to elude cellular repair responses and to potentially interact with other-than-DNA targets, thus affording a novel activity profile.
Starting from those assumptions and considering the promising results obtained of our research group in the synthesis of aminomethylimidazole based dichloride platinum complexes,3 we synthesised a series of cationic triamine platinum compounds of general formula [Pt(N-N’)N’Cl]X- where N-N’ is an aminomethylimidazole ligand and the N’ an imidazole ring, both bearing the same alkyl group at the N1 position. The resulting platinum complexes were analytically characterized and biologically evaluated on different cancer cell lines known for their aggressive behaviour (triple negative breast cancer)4 and for their poor sensitivity to the common cisplatin chemotherapy. Moreover, several in vitro assays were performed in order to better define their antitumor activity and target selectivity
The role of stochasticity in a model of retinal angiogenesis
No full textThe macroscopic behaviour of dissipative stochastic partial differential equations usually can be
described by a finite-dimensional system. This article proves that a macroscopic reduced model may
be constructed for stochastic reaction–diffusion equations by artificially separating the system into two
distinct slow and fast time parts. An averaging method and a deviation estimate show that the macroscopic
reduced model should be a stochastic ordinary equation that includes emergent random effects
transmitted from the microscopic scales due to the non-linear interaction. Numerical simulations of an
example stochastic reaction–diffusion equation verifies the predictions of this stochastic modelling theory.
This theory empowers us to better model the dynamics of complex stochastic systems on a large time
scale
Randomness in self-organized phenomena. A case study: retinal angiogenesis
No full textThis note presents a review of recent work by the authors on angiogenesis, as a case study for analyzing the role of randomness in the formation of biological patterns. The mathematical description of the formation of new vessels is presented, based on a system of stochastic differential equations, coupled with a branching process, both of them driven by a set of relevant chemotactic underlying fields. A discussion follows about the possible reduction of complexity of the above approach, by mean field approximations of the underlying fields. The crucial role of randomness at the microscale is observed in order to obtain nontrivial realistic vessel networks
Catalytic strategies for the synthesis of carnosine derivatives
Full text linkL-Carnosine is a naturally occurring endogenous dipeptide formed by the combination of β-alanine and L-histidine, particularly in tissues with high oxidative metabolism such as muscles and the brain. By neutralizing free radicals and reducing oxidative stress—factors associated with various age-related conditions—it is believed to offer cellular protection1. The Global L-Carnosine Market size was estimated to be around USD 35.87 million in 2022, with projections indicating future growth at a compound annual growth rate of 6.45% until 2030. Thus, the development of synthetic methods able to afford L-Carnosine and its derivatives in enantiopure form is attracting interest and investments from both academia and industry. The contribution offers both the points of view applied to the attempt to achieve such a goal. The first part was focused on the development of a second-generation process for the synthesis of L-Carnosine. A series of nitrile precursor reduction studies was performed utilized gaseous H2 and commercially available (Pd, Rh, etc). As final scope, the optimization of the reaction conditions was performed, including a method for the isolation of the product as chromatographic separation and/or crystallization of the corresponding salt. Asymmetric hydrogenation using transition metal catalysts is a significant transformation in both academia and industry. Its high efficiency, atom economy, and broad substrate scope make this methodology appealing for both fields. In the second part, starting from an unsaturated precursor, different rhodium catalysts based on non-commercially available diphosphine were applied to the synthesis of enantiopure L-Carnosine derivatives with e.e. up to 95%
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