RESUMEN
Accumulation of advanced glycation end-products (AGEs) in the brain contributes significantly to cognitive impairment in patients with diabetes by disrupting the post-mitotic state of neuronal cells, thereby triggering ectopic cell cycle re-entry (CCR) and subsequent neuronal apoptosis. Cinnamaldehyde (CINA), a potential mitigator of cognitive impairment due to its blood glucose-lowering properties, warrants exploration for its role in counteracting diabetes-related neurological damage. In this study, we examined the neuroprotective effect of CINA on AGE-damaged SH-SY5Y human neuroblastoma cells differentiated in vitro. We investigated the impact of CINA on AGE-induced neuronal CCR and apoptosis, finding that it substantially suppressed aberrant DNA replication, precluded cells from entering the mitotic preparatory phase, and diminished apoptosis. Additionally, CINA inhibited the expression of eIF4E without altering S6K1 phosphorylation. These findings indicate that CINA safeguards neuronal cells from AGE-related damage by preventing abnormal CCR, preserving the post-mitotic state of neuronal cells, and reducing AGE-induced apoptosis, potentially through the inhibition of eIF4E-controlled cell proliferation. Our results highlight the prospective utility of CINA in managing diabetic neuropathy.
Asunto(s)
Acroleína , Apoptosis , Ciclo Celular , Productos Finales de Glicación Avanzada , Neuronas , Fármacos Neuroprotectores , Acroleína/análogos & derivados , Acroleína/farmacología , Humanos , Productos Finales de Glicación Avanzada/metabolismo , Apoptosis/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Ciclo Celular/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Línea Celular Tumoral , Neuropatías Diabéticas/prevención & control , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/tratamiento farmacológico , Replicación del ADN/efectos de los fármacos , Fosforilación/efectos de los fármacosRESUMEN
Actinide metallacyclic chemistry has been of interest due to its involvement in various chemical processes. However, fundamental understanding on the key species, actinide metallacyclic complexes, is limited to metallacyclopropenes whereas little is known about the actinide metallacyclopropynes presumably due to their unusual high reactivity. Herein, we report the preparation of a thorium metallacyclopropyne complex (η2-C ≡ C)ThCl3- in the gas phase by using electrospray ionization mass spectrometry, and it is generated via a single-ligand strategy through sequential losses of CO2 and HCl from the monopropynoate precursor (HC ≡ CCO2)ThCl4- upon collision-induced dissociation. Alternatively, the dual-ligand strategy involving consecutive losses of two CO2 and one C2H2 from the dipropynoate precursor (HC ≡ CCO2)2ThCl3- works as well. According to the reactivity experiments and theoretical calculations, (η2-C ≡ C)ThCl3- possesses a dianionic ligand C22- coordinated to the Th(IV) center in a side-on fashion. Further bonding analysis demonstrates the presence of a triple bond between the two C atoms, and the Th 5 f orbitals are significantly involved in the Th-(C ≡ C) bonding. A Th metallacyclopropyne structure is thus established for (η2-C ≡ C)ThCl3-.
RESUMEN
The lanthanide(III) cyanobenzyne complexes (η2-4-CNC6H3)LnCl2- (Ln = La-Lu except Eu; Pm was not examined) were generated in the gas phase using an electrospray ionization mass spectrometry coupled with collision-induced dissociation (CID) technique. For all lanthanides except Sm, Eu, and Yb, (4-CNC6H3)LnCl2- can be generated either via a single-ligand strategy through consecutive CO2 and HCl losses of (4-CNC6H4CO2)LnCl3- or via a dual-ligand strategy through successive CO2/C6H5CN or 4-CNC6H4CO2H and CO2 losses of (4-CNC6H4CO2)2LnCl2-. For Sm and Yb, although only reduction products LnCl3- were formed upon CID of (4-CNC6H4CO2)LnCl3-, (4-CNC6H3)LnCl2- were obtained via the dual-ligand strategy without the appearances of other products. CID of (4-CNC6H4CO2)EuCl3- and (4-CNC6H4CO2)2EuCl2- gave EuCl3- and the cyanophenyl complex (4-CNC6H4)EuCl2-, respectively, in both of which the +III oxidation state of Eu was reduced to +II. Density functional theory (DFT) calculations reveal that (4-CNC6H3)LnCl2- are formally described as Ln(III) cyanobenzyne complexes, (η2-4-CNC6H3)LnCl2-, with the dianionic cyanobenzyne ligand (4-CNC6H32-) coordinating to the Ln(III) centers through two Ln-C σ bonds, which is in accordance with their reactivities toward water. Benzyne and substituted benzyne complexes (XC6H3)LuCl2- (X = H, 3-CN, 4-F, 4-Cl, and 4-CH3) were also synthesized in the gas phase via the single- and dual-ligand strategies.