Elucidating the chemiexcitation of dioxetanones by replacing the peroxide bond with S-S, N-N and C-C bonds

Dioxetanone is one of the prototypical cyclic peroxide intermediates in several chemiluminescent and bioluminescent systems, in which thermolysis reactions allow efficient singlet chemiexcitation. While the chemiexcitation mechanism of dioxetanone and peroxide intermediates is still far from understood, the presence of a peroxide bond that undergoes bond breaking has been found to be a constant. Here we have addressed the following questions: can other non-peroxide bonds lead to chemiexcitation and, if not, can the differences between dioxetanone and non-peroxide derivatives help to elucidate their chemiexcitation mechanism? To this end, we have used a reliable TD-DFT approach to model the thermolysis and chemiexcitation of a model dioxetanone and its three other non-peroxide derivatives. The results showed that only the dioxetanone molecule could lead to chemiluminescence as it is the only one for which thermolysis is energetically favorable and provides a pathway for singlet chemiexcitation. Finally, the chemiexcitation of the model dioxetanone is explained by its access, during thermolysis, to a biradical region where the ground and excited states are degenerate. This occurs due to an increased interaction between the reaction fragments, which extends the biradical regions and delays the rupture of the peroxide ring

Vasoactive Biomarkers in Patients With Vasovagal Syncope During Head-Up Tilt Test: A Case-Control Study

Vasovagal syncope (VVS) is the most common cause of syncope. Some stages of its pathophysiological mechanisms remain unclear. Vasoactive substances such as nitric oxide metabolites (NOx) and endothelin (ET) may be involved during acute orthostatic stress.To analyze plasma changes in NOx and ET and heart rate variability (HRV) in the supine positions (T1) and during the head-up tilt test (HUTT) (T2), in patients with VVS (case group) and control group.Thirty-seven patients (17 in the case group and 20 in the control group), matched for age and sex (mean aged 31.8 years) underwent HUTT with simultaneous HRV recording and venipuncture. Blood samples were collected during phases T1 and T2 and the analysis was performed without knowledge of the HUTT result.In the total sample, there was an increase in NOx values (P = .014), however there was no increase in ET values from phase T1 to phase T2. Patients with VVS tended to increase plasma NOx values (P = .057) and had significantly higher plasma values compared to ET (P = .033) between phases T1 to T2. In the control group, there was no significant change in the values of these vasoactive substances. Regarding HRV, there were a decrease in the component HF (high frequency) and increased of the LF (low frequency)/HF ratio during HUTT.There was an increase in ET during HUTT occurred only in the case group. These patients are more likely to have an imbalance between antagonistic vasoactive biomarkers during orthostatic stress.© The Author(s) 2022

Investigation of the Anticancer and Drug Combination Potential of Brominated Coelenteramines toward Breast and Prostate Cancer

Cancer is a very challenging disease to treat, both in terms of therapeutic efficiency and harmful side effects, which continues to motivate the pursuit for novel molecules with potential anticancer activity. Herein, we have designed, synthesized, and evaluated the cytotoxicity of different brominated coelenteramines, which are metabolic products and synthesis precursors of the chemi-/bioluminescent system of marine coelenterazine. The evaluation of the anticancer potential of these molecules was carried out for both prostate and breast cancer, while also exploring their potential for use in combination therapy. Our results provided further insight into the structure-activity relationship of this type of molecule, such as their high structural specificity, as well highlighting the 4-bromophenyl moiety as essential for the anticancer activity. The obtained data also indicated that, despite their similarity, the anticancer activity displayed by both brominated coelenteramines and coelenterazines should arise from independent mechanisms of action. Finally, one of the studied coelenteramines was able to improve the profile of a known chemotherapeutic agent, even at concentrations in which its anticancer activity was not relevant. Thus, our work showed the potential of different components of marine chemi-/bioluminescent systems as novel anticancer molecules, while providing useful information for future optimizations

Free radical scavenging activity of Pterogyne nitens Tul. (Fabaceae)

As part of our ongoing research on antioxidant agents from Brazilian flora, twenty extracts and fractions obtained from Pterogyne nitens Tulasne (Fabaceae) were screened for free radical scavenging activity by using ABTS [2,2’-azinobis(3-ethylenebenzothiazoline-6-sulfonic acid)] and DPPH (2,2-diphenyl-1-picrylhydrazyl-hydrate) radicals colorimetric assay and -carotene bleaching test. The strongest activity was found in ethyl acetate fraction from the stem barks, exhibiting IC50 values (inìg/ml) of 2.10 ± 0.1 and 10.2 ± 0.3 on ABTS•+ and DPPH•, respectively. Additionally, chromatographic fractionation of stem barks yielding myricetin, quercitrin and mirycetrin, three flavonols with remarkable antioxidant activity

Target-Oriented Synthesis of Marine Coelenterazine Derivatives with Anticancer Activity by Applying the Heavy-Atom Effect

Photodynamic therapy (PDT) is an anticancer therapeutic modality with remarkable advantages over more conventional approaches. However, PDT is greatly limited by its dependence on external light sources. Given this, PDT would benefit from new systems capable of a light-free and intracellular photodynamic effect. Herein, we evaluated the heavy-atom effect as a strategy to provide anticancer activity to derivatives of coelenterazine, a chemiluminescent single-molecule widespread in marine organisms. Our results indicate that the use of the heavy-atom effect allows these molecules to generate readily available triplet states in a chemiluminescent reaction triggered by a cancer marker. Cytotoxicity assays in different cancer cell lines showed a heavy-atom-dependent anticancer activity, which increased in the substituent order of hydroxyl < chlorine < bromine. Furthermore, it was found that the magnitude of this anticancer activity is also dependent on the tumor type, being more relevant toward breast and prostate cancer. The compounds also showed moderate activity toward neuroblastoma, while showing limited activity toward colon cancer. In conclusion, the present results indicate that the application of the heavy-atom effect to marine coelenterazine could be a promising approach for the future development of new and optimized self-activating and tumor-selective sensitizers for light-free PDT

HLA-C stability and AIDS progression

HLA-C stability influence AIDS progressio