120 research outputs found
PROGETTAZIONE, SINTESI, VALUTAZIONE BIOLOGICA E STUDI DI QSAR DI SISTEMI POLICICLICI AZOTATI QUALI ANTAGONISTI PER I RECETTORI ADENOSINICI
2002/2003XVI Ciclo1976Versione digitalizzata della tesi di dottorato cartacea
The current status of pharmacotherapy for the treatment of Parkinson's disease: transition from single-target to multitarget therapy
Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons. Motor features such as tremor, rigidity, bradykinesia and postural instability are common traits of PD. Current treatment options provide symptomatic relief to the condition but are unable to reverse disease progression. The conventional single-target therapeutic approach might not always induce the desired effect owing to the multifactorial nature of PD. Hence, multitarget strategies have been proposed to simultaneously target multiple proteins involved in the development of PD. Herein, we provide an overview of the pathogenesis of PD and the current pharmacotherapies. Furthermore, rationales and examples of multitarget approaches that have been tested in preclinical trials for the treatment of PD are also discussed
8-Methyl-2-[4-(trifluoromethyl)phenyl]-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine methanol disolvate
In the title compound, C14H10F3N7·2CH4O, the heterocyclic ring system is essentially planar (r.m.s. deviation = 0.009 Å) and makes a dihedral angle of 6.91 (8)° with the attached benzene ring. In the crystal, the main molecules form centrosymmetric R
2
2(8) dimers via pairs of N—H⋯N hydrogen bonds between the amino groups and pyrimidine N atoms. One of the independent methanol molecules and its inversion equivalent are linked to the dimers via O—H⋯N and N—H⋯O hydrogen bonds, forming R
4
4(16) graph-set motifs. The dimers along with the hydrogen-bonded methanol molecules are stacked along the a axis, with π–π interactions between the pyrazole and triazole rings [centroid–centroid distance = 3.4953 (10) Å]
Graphene for Controlled and Accelerated Osteogenic Differentiation of Human Mesenchymal Stem Cells
Modern tissue engineering strategies combine living cells and scaffold
materials to develop biological substitutes that can restore tissue functions.
Both natural and synthetic materials have been fabricated for transplantation
of stem cells and their specific differentiation into muscles, bones and
cartilages. One of the key objectives for bone regeneration therapy to be
successful is to direct stem cells' proliferation and to accelerate their
differentiation in a controlled manner through the use of growth factors and
osteogenic inducers. Here we show that graphene provides a promising
biocompatible scaffold that does not hamper the proliferation of human
mesenchymal stem cells (hMSCs) and accelerates their specific differentiation
into bone cells. The differentiation rate is comparable to the one achieved
with common growth factors, demonstrating graphene's potential for stem cell
research.Comment: 34 pages, 11 figures, 1 table, submitte
(4Z,6Z,12Z,14Z)-2,10-Dimethyl-2,8,10,16-tetrahydrodipyrazolo[3,4-e:3′,4′-l][1,2,4,8,9,11]hexaazacyclotetradecine-4,12-diamine
The title compound, C12H16N12, is a centrosymmetric molecule which comprises of a hexaaza[14]annulene macrocyclic ring fused with two pyrazole rings. The macrocyclic ring is essentially planar, with an r.m.s. deviation of 0.0381 Å. The electron pairs of the amino groups are delocalized with the conjugated system of the macrocycle. Strong intramolecular N—H⋯N hydrogen bonds arranged in an S
2
2(10) graph-set motif are present in the macrocyclic ring. In the crystal, the amino groups act as donors for intermolecular N—H⋯N interactions with the N atoms of the heterocyclic system, forming a network of two types of extended chains oriented parallel to the [101] and [011] directions. The crystal packing is also stabilized by weak intermolecular C—H⋯N hydrogen bonds formed between pyrazole C—H groups and N atoms of the macrocyclic ring, running in the [10] direction
Dual-functional iron oxide nanoparticles coated with polyvinyl alcohol/5-fluorouracil/zinc-aluminium-layered double hydroxide for a simultaneous drug and target delivery system
Iron oxide nanoparticles are suitable for biomedical applications owing to their ability to anchor to various active agents and drugs, unique magnetic properties, nontoxicity, and biocompatibility. In this work, the physico-chemical and magnetic properties, as well as the cytotoxicity, of Fe3O4 nanoparticles coated with a polymeric carrier and loaded with a 5-fluorouracil (5-FU) anti-cancer drug are discussed. The synthesized Fe3O4 nanoparticles were coated with polyvinyl alcohol and Zn/Al-layered double hydroxide as the drug host. The XRD, DTA/TG, and FTIR analyzes confirmed the presence of the coating layer on the surface of nanoparticles. The results showed a decrease in saturation magnetization of bare Fe3O4 nanoparticles after coating with the PVA/5FU/Zn/Al-LDH layer. In addition, the presence of the coating prevented the agglomeration of nanoparticles. Furthermore, the pseudo-second-order equation governed the kinetics of drug release. Finally, the coated nanoparticles showed stronger activity against liver cancer cells (HepG2) compared to that of the naked 5-FU drug, and displayed no cytotoxicity towards 3T3 fibroblast cell lines. The results of the present study demonstrate the potential of a nano delivery system for cancer treatment
4-Hydrazino-1-methylpyrazolo[3,4-d]pyrimidine
The title compound, C6H8N6, crystallizes as an N—H⋯N hydrogen-bond-linked dimer of two almost identical molecules in the asymmetric unit. Both of the molecules are almost planar (rms deviations of 0.0186 and 0.0296 Å in the two molecules) and their hydrazino groups are turned towards the pyrazole rings. The dimers are arranged into chains via intermolecular N—H⋯N hydrogen bonds between the hydrazino groups and the N atoms of the pyrimidine rings of both types of the molecules, linking the molecules into a C(7) graph-set motif along [100]. The methyl groups and the N atoms of the pyrazole rings form weak C—H⋯N hydrogen bonds, which connect chains of the dimers in a C(4) motif parallel to [100]
- …