Tetrahydroindazolone substituted 2-aminobenzamides as fluorescent probes: switching metal ion selectivity from zinc to cadmium by interchanging the amino and carbamoyl groups on the fluorophore.

Three fluorescent probes CdABA', CdABA and ZnABA', which are structural isomers of ZnABA, have been designed with N,N-bis(2-pyridylmethyl) ethylenediamine (BPEA) as chelator and 2-aminobenzamide as fluorophore. These probes can be divided into two groups: CdABA, CdABA' for Cd(2+) and ZnABA, ZnABA' for Zn(2+). Although there is little difference in their chemical structures, the two groups of probes exhibit totally different fluorescence properties for preference of Zn(2+) or Cd(2+). In the group of Zn(2+) probes, ZnABA/ZnABA' distinguish Zn(2+) from Cd(2+) with F(Zn)(2+)-F(Cd)(2+) = 1.87-2.00. Upon interchanging the BPEA and carbamoyl groups on the aromatic ring of the fluorophore, the structures of ZnABA/ZnABA' are converted into CdABA/CdABA'. Interestingly, the metal ions selectivity of CdABA/CdABA' was switched to discriminate Cd(2+) from Zn(2+) with F(Cd)(2+)-F(Zn)(2+) = 2.27-2.36, indicating that a small structural modification could lead to a remarkable change of the metal ion selectivity. (1)H NMR titration and ESI mass experiments demonstrated that these fluorescent probers exhibited different coordination modes for Zn(2+) and Cd(2+). With CdABA' as an example, generally, upon addition of Cd(2+), the fluorescence response possesses PET pathway to display no obvious shift of maximum λ(em) in the absence or presence of Cd(2+). However, an ICT pathway could be employed after adding Zn(2+) into the CdABA' solution, resulting in a distinct red-shift of maximal λ(em).

Effects of pravastatin on myocardial connexin 43, IFN-gamma and IL-10 expressions in a murine model of viral myocarditis induced by Coxsackievirus B3 / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effects of pravastatin on myocardial connexin 43 (Cx43), IFN-gamma and IL-10 expressions in a murine model of viral myocarditis (VMC) induced by Coxsackievirus B3.</p><p><b>METHODS</b>Four-week-old male Balb/c mice were inoculated intraperitoneally with Coxsackievirus B3 and then randomly received saline (group A, n = 12), low dose pravastatin (40 mg.kg(-1).d(-1), group B, n = 12) and high dose pravastatin (80 mg.kg(-1).d(-1), group C, n = 12) for 14 days. Another group of mice were injected with Eagle's solution and treated with saline (group D, n = 12) or high dose pravastatin (80 mg.kg(-1).d(-1), group E, n = 12). After 14 days treatments, serum IFN-gamma, IL-10 were assayed using ELISA, myocardium IFN-gamma, IL-10 and Cx43 mRNA levels were measured by real-time PCR, myocardium expression of Cx43 was also determined by immunohistochemistry staining method on cardiac myocytes.</p><p><b>RESULTS</b>Pravastatin dose-dependently upregulated Cx43 proteins on membrane of myocardial cells (group A: 0.16 +/- 0.06, group B: 4.55 +/- 0.73 and group C: 5.21 +/- 0.42, P < 0.01 vs. group A) and Cx43 mRNA expression (group A: 1.000 +/- 0.127, group B: 1.320 +/- 0.096, group C: 1.550 +/- 0.126, P < 0.05 vs. group A), IL-10 mRNA expression (group A: 1.000 +/- 0.031, group B: 1.810 +/- 0.029, group C: 2.140 +/- 0.032, P < 0.05 vs. group A) while down-regulated IFN-gamma mRNA (group A: 1.000 +/- 0.061, group B: 0.603 +/- 0.063, group C: 0.333 +/- 0.071, P < 0.01 vs. group A). Serum IFN-gamma, IL-10 concentrations changed in the same direction as myocardial mRNA levels of IFN-gamma, IL-10 post pravastatin treatments.</p><p><b>CONCLUSION</b>Pravastatin treatments upregulated expressions of Cx43 at mRNA and protein levels and improved the INF-gamma/IL-10 balance which might be the working mechanisms for pravastatin-mediated anti-VMC and anti-arrhythmia effects in this VMC model.</p>