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Background: In recent decades, there has been a startling rise in the number of cancer patients worldwide, which has led to an amazing upsurge in the development of novel anticancer treatment candidates. On a positive note, arylpiperazines have garnered attention in cancer research due to their potential as scaffolds for developing anticancer agents. These compounds exhibit a diverse array of biological activities, including cytotoxic effects against cancer cells. Indeed, one of the key advantages of arylpiperazines lies in their ability to interact with various molecular targets implicated in cancer pathogenesis. Aim: Here, we focus on the chemical structures of several arylpiperazine derivatives, highlighting their anti-proliferative activity in different tumor cell lines. The modular structure, diverse biological activities, and potential for combination therapies of arylpiperazine compounds make them valuable candidates for further preclinical and clinical investigations in the fight against cancer. Conclusion: This review, providing a careful analysis of different arylpiperazines and their biological applications, allows researchers to refine the chemical structures to improve potency, selectivity, and pharmacokinetic properties, thus advancing their therapeutic potential in oncology. [ABSTRACT FROM AUTHOR]

In this study, a new and straightforward process for the preparation of budesonide 21-phosphate (Bud-21P) and its disodium salt (Bud-21P-Na2) is described. The method results in a yield comparable to those obtained by diphosphoryl chloride, but it is more manageable, less expensive, and safer. The new compounds are characterized by better water solubility compared to the parent compound. Moreover, they have been evaluated for their anti-inflammatory activity and the obtained results clearly evidence that Bud-21P and Bud-21P-Na2 retained anti-inflammatory activity like the parent compound budesonide (Bud) in mice with cutaneous induced edema. [ABSTRACT FROM AUTHOR]

Introduction: The human umbilical artery (HUA), rat-isolated right atrium, and rat-isolated vas deferens present a basal release of 6-nitrodopamine (6-ND). The basal release of 6-ND from these tissues was significantly decreased (but not abolished) when the tissues were pre-incubated with Nω-nitro-L-arginine methyl ester (L-NAME). Methods: In this study, the effect of the pharmacological modulation of the redox environment on the basal release of 6-ND was investigated. The basal release of 6-ND was measured using Liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results and Discussion: Pre-incubation (30min) of the tissues with GKT137831 (1 µM) caused a significant increase in the basal release of 6-ND from all tissues. In the HUA, pre-incubation with diphenyleneiodonium (DPI) (100 µM) also caused significant increases in the basal release of 6-ND. Preincubation of the HUA with hydrogen peroxide (H2O2) (100 µM) increased 6-ND basal release, whereas preincubation with catalase (1,000 U/mL) significantly decreased it. Pre-incubation of the HUA with superoxide dismutase (SOD) (250 U/mL; 30min) also significantly increased the basal release of 6-ND. Preincubation of the HUA with either allopurinol (100 µM) or uric acid (1mM) had no effect on the basal release of 6-ND. Pre-treatment of the HUAwith L-NAME (100 µM) prevented the increase in the basal release of 6-ND induced by GKT137831, diphenyleneiodonium, and H2O2. The results obtained indicate amajor role of endogenous H2O2 and peroxidases as modulators of 6-ND biosynthesis/release and a lack of peroxynitrite contribution. [ABSTRACT FROM AUTHOR]

This document is an editorial from the International Journal of Molecular Sciences discussing the role of hydrogen sulfide (H2S) in physiological and pathological processes. The article highlights the positive effects of H2S in various processes such as inflammation, hypertension, oxidation, metabolic disorders, neuromodulation, and tumor progression. It also discusses the natural sources of H2S, including garlic-derived compounds and vegetables from the Brassicaceae family. The editorial presents research on natural and synthetic H2S-donating compounds and their pharmacological effects, including antioxidant properties, anti-inflammatory effects, regulation of the immune system, cardioprotection, and cancer prevention. Additionally, it explores the development of novel molecular hybrids combining H2S donors with existing drugs for potential therapeutic applications. [Extracted from the article]

This study presents the validation of a sensitive method for the determination of 6‐nitrodopa, 6‐nitrodopamine, 6‐nitroadrenaline and 6‐cyanodopamine in Krebs–Henseleit solution by LC–MS/MS with ESI+. HRMS was used to precisely characterize the structures of the fragment ions. The method was applied to investigate the catecholamine basal release from rabbit isolated atria and ventricles. The atria and ventricles were suspended separately in a 5 ml organ bath containing Krebs–Henseleit solution with ascorbic acid (3 mM), gassed (95%O2/5%CO2) at 37°C for 30 min. Strata‐X 33 μm SPE cartridges were employed for the extraction of the catecholamines and the internal standard 6‐nitrodopamine‐d4. The catecholamines were separated employing a 150 × 3 mm Shim‐pack GIST C18‐AQ (3 mm particle size), placed in an oven at 40°C and perfused by 65% of mobile phase A (MeCN/H2O; 90/10, v/v) + 0.4% CH3COOH and 35% mobile phase B (deionized H2O) + 0.2% CH2O2 at 320 μl/min in isocratic mode. The method was linear at 0.1–20 ng/ml. The method was used to identify for the first‐time basal release of the three nitrocatecholamines mentioned above and a member of a novel class of catecholamines, the cyanocatecholamines. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is particularly produced in the skin, where it participates in the regulation of inflammation, pruritus, cytoprotection, scarring, and angiogenesis. In this study, we compared the effects of dexamethasone (Dex) with two H2S-releasing Dex derivatives in a murine model of atopic dermatitis (AD) induced by topical application of 2,4-dinitrochlorobenzene (DNCB). After sensitization with DNCB, the animals were topically treated for five consecutive days with either the H2S-releasing compounds 4-hydroxy-thiobenzamide (TBZ) and 5-(p-hydroxyphenyl)-1,2-dithione-3-thione (ADT-OH), Dex, or the derivatives Dex-TBZ or Dex-ADT. Topical treatment with equimolar doses of either Dex, Dex-TBZ, or Dex-ADT resulted in similar reductions in dermatitis score, scratching behavior, edema, eosinophilia, splenomegaly, and histological changes. In contrast with Dex, the H2S-releasing derivatives prevented IL-4 elevation and oxidative modification of skin proteins. On an equimolar dose basis, Dex-TBZ, but not Dex-ADT, promoted the elevation of endogenous H2S production and GPx activity. Neither Dex-TBZ nor Dex-ADT decreased GR activity or caused hyperglycemia, as observed with Dex treatment. We conclude that the presence of H2S-releasing moieties in the Dex structure does not interfere with the anti-inflammatory effects of this corticosteroid and adds beneficial therapeutical actions to the parent compound. [ABSTRACT FROM AUTHOR]

We recently identified 6-nitrodopamine and other nitro-catecholamines (6-nitrodopa, 6-nitroadrenaline), indicating that the endothelium has the ability to nitrate the classical catecholamines (dopamine, noradrenaline, and adrenaline). In order to investigate whether drugs could be subject to the same nitration process, we synthesized 4-nitro- and 7-nitropropranolol as probes to evaluate the possible nitration of the propranolol by the endothelium. The separation of the enantiomers in very high yields and excellent enantiopurity was achieved by chiral HPLC. Finally, we used Riguera's method to determine the absolute configuration of the enantiomers, through double derivatization with MPA and NMR studies. [ABSTRACT FROM AUTHOR]