Goldoni Fernanda Capitanio, Benvenutti Larissa, Nunes Roberta, Vaz Carlos Rafael, Garcia Louise, Furtado Keyla, Dos Santos Bubniak Lorena, de Campos Buzzi Fátima, Corrêa Rogério, Quintão Nara Lins Meira, Santin José Roberto
Postgraduate Program in Pharmaceutical Science, Universidade Do Vale Do Itajaí (UNIVALI), 458, Bloco F6, ECS, Sala 316, CEP, Itajaí, SC, 88302-901, Brazil.
Pharmacy Course, School of Health Sciences, Universidade Do Vale Do Itajaí (UNIVALI), Itajaí, SC, Brazil.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May;398(5):5677-5691. doi: 10.1007/s00210-024-03653-z. Epub 2024 Nov 27.
Pyrazolines are compounds that have been studied for their strong biological potential and structure diversity. Several studies demonstrated their biological effectiveness, highlighting their anti-inflammatory potential. This study aimed to evaluate the physicochemical profile, the safety, and the anti-inflammatory effects of four pyrazolines (PH0, PH3, PH4, and PH7). Initially, in silico analysis were performed on SwissADME and QSAR Toolbox platforms. The anti-inflammatory activity was assessed by in vitro and in vivo methodologies. Neutrophils collected from mice peritoneum and macrophages immortalized cell line (Raw 264.7) were stimulated with lipopolysaccharide (LPS), and subsequent measurement of nitric oxide (NO) and IL-1β, TNF, and IL-6 cytokines were performed by ELISA method. The effect on cell migration was evaluated by chemotaxis assay. The effect on efferocytosis was investigated using senescent neutrophils and macrophages from mice's bone marrow. The in silico results suggest suitable properties for a pharmacological prototype for oral administration, with no significant toxic effects. All compounds significantly reduced NO levels, as well as levels of IL-1β, TNF, and IL-6 cytokines. Also, they were able to reduce cell migration and increase efferocytosis. The in vivo air pouch model confirmed the effects of pyrazolines on cell kinetics and on the levels of cytokines (IL-1β and TNF) on the air pouch lavage. All of the pyrazolines evaluated showed to have positive effects on mechanisms that modulate the inflammatory response. Furthermore, the in silico analysis suggests that chemical changes in the structure can lead to improvement of the biological and pharmacokinetics proprieties.
吡唑啉是一类因其强大的生物活性和结构多样性而受到研究的化合物。多项研究证实了它们的生物有效性，突出了其抗炎潜力。本研究旨在评估四种吡唑啉（PH0、PH3、PH4和PH7）的理化性质、安全性及抗炎作用。首先，在SwissADME和QSAR Toolbox平台上进行了计算机模拟分析。通过体外和体内方法评估抗炎活性。用脂多糖（LPS）刺激从小鼠腹腔收集的中性粒细胞和永生化巨噬细胞系（Raw 264.7），随后通过ELISA法检测一氧化氮（NO）以及IL-1β、TNF和IL-6细胞因子。通过趋化性试验评估对细胞迁移的影响。使用来自小鼠骨髓的衰老中性粒细胞和巨噬细胞研究对胞葬作用（efferocytosis）的影响。计算机模拟结果表明，这些化合物具有作为口服给药药理原型的合适性质，且无明显毒性作用。所有化合物均能显著降低NO水平以及IL-1β、TNF和IL-6细胞因子的水平。此外，它们还能够减少细胞迁移并增强胞葬作用。体内气囊模型证实了吡唑啉对细胞动力学以及气囊灌洗中细胞因子（IL-1β和TNF）水平的影响。所有评估的吡唑啉均对调节炎症反应的机制具有积极作用。此外，计算机模拟分析表明，结构上的化学变化可导致生物学和药代动力学性质的改善。
