RESUMEN
We have utilized reversible covalent bonding to expand the accessible states of a molecular switch. Introducing a hydroxyl group onto the donor moiety of a donor-acceptor Stenhouse adduct (DASA) imparts an acidity response by forming an oxazolidine ring through intramolecular nucleophilic addition. Furthermore, we observed distinct color changes under cryogenic conditions, extending the thermal responsiveness beyond the cyclization equilibrium observed at elevated temperatures. These unique responses present promising prospects for diverse applications compared to traditional photoinduced binary isomerization.
RESUMEN
The magnetic bistability of spin-crossover (SCO) materials is highly appealing for applications as molecular switches and information storage. However, switching of the spin state around room temperature remains challenging. In this work, we reported the successful manipulation of the spin states of two iron(II) complexes (1-Fe and 2-Fe) based on pyridylacylhydrazone ligands in manifold ways. Both complexes are stabilized in the low-spin (LS) state at room temperature because of the strong ligand-field strength imposed by the ligands. 2-Fe shows thermoinduced SCO above room temperature with a very large and reproducible hysteresis (>50 K), while 1-Fe remains in the LS state up to 400 K. Acidity-driven spin-state switching of the two complexes was achieved at room temperature as a result of the complex dissociation and release of iron(II) in its high-spin (HS) state. Recovery of the complex is feasible upon further alkalization treatment in the case of 1-Fe, allowing bidirectional modulation of the spin state of the metal center. Light-driven one-way switching from LS to HS is also achieved by virtue of E-to-Z isomerization at the CâN double bond, which results in dissociation of the complex because of the poor binding affinity in the Z configuration.
RESUMEN
The high toxicity of actinomycin D (Act D) severely limits its use as a first-line chemotherapeutic agent in the clinic. Actinomycin V (Act V), an analog of Act D, exhibited strong anticancer activity in our previous studies. Here, we provide evidence that Act V has less hepatorenal toxicity than Act D in vitro and in vivo, associated with the reactive oxygen species (ROS) pathway. Compared to Act D, Act V exhibited considerably stronger sensitivity for cancer cells and less toxicity to human normal liver LO-2 and human embryonic kidney 293T cells using the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay. Notably, Act V caused less damage to both the liver and kidney than Act D in vivo, indicated by organ to body weight ratios, as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum creatinine (Scr) levels. Further experiments showed that the ROS pathway is involved in Act V-induced hepatorenal toxicity. Act V generates ROS and accumulates malondialdehyde (MDA), reducing levels of superoxide dismutase (SOD) and glutathione (GSH) in LO-2 and 293T cells. These findings indicate that Act V induces less hepatorenal toxicity than Act D in vitro and in vivo and merits further development as a potential therapeutic agent for the treatment of cancer.
Asunto(s)
Antibióticos Antineoplásicos/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Dactinomicina/análogos & derivados , Dactinomicina/toxicidad , Enfermedades Renales/inducido químicamente , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Relación Dosis-Respuesta a Droga , Células HEK293 , Humanos , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , RatonesRESUMEN
OBJECTIVE: To observe the therapeutic effects of Jingyuankang capsules for leukopenia in AIDS patients. METHODS: In this randomized double-blind trial, 58 patients orally took Jingyuankang capsule, analog Leucogen tablet and the HAART (highly active anti-retroviral therapy) drugs, and the other 58 patients took Leucogen tablet, analog Jingyuankang capsule and the HAART drugs all for 6 months, during which the peripheral hemogram was periodically examined to observe the therapeutic effects of Jingyuankang capsule for leukopenia of the AIDS patients. RESULTS: With good therapeutic effect for leukopenia of the AIDS patients, Jingyuankang capsule can enhance leukocyte level as effective as Leucogen tablet in treating grade I and grade II leukopenia, and more effectively than Leucogen tablet in treating grade III leukopenia. No toxic side-effects and adverse reactions were found during the treatment and in the follow-up visit. CONCLUSION: Jingyuankang capsule can effectively treat leukopenia of the AIDS patients.