Synthesis and Evaluation of Novel D-ring Substituted Steroidal Pyrazolines as Potential Anti-inflammatory Agents

Publication date: Available online 2 April 2019Source: SteroidsAuthor(s): Xiaorui Cai, Shulin Zhao, De Cai, Jinhong Zheng, Zhiwei Zhu, Duncan Wei, Zhiwei Zheng, Huide Zhu, Yicun ChenAbstractTo identify new potential anti-inflammatory agents, a number of novel steroidal derivatives with nitrogen heterocyclic side chains 4a-4l were synthesized and evaluated for their anti-inflammatory effects in activated RAW 264.7 macrophage cells. The synthesis scheme involves two steps, Claisen-Schmidt condensation with the corresponding pregnenolone and aromatic aldehydes as the first step followed by nucleophilic addition of thiosemicarbazide across an α, β-unsaturated carbonyl as a later step. Compound structures were confirmed by 1H-NMR, 13C-NMR, HRMS, and IR. The compounds were assayed to test their anti-inflammatory effects in activated RAW 264.7 cells. Compound 4g, 3β-hydroxy-pregn-5-en-17β-yl-5’-(m-fluorophenyl)-4’, 5’-dihydro-1’-carbothioic acid amido pyrazole , was identified as the most potent anti-inflammatory agent of the analysed compounds, with an IC50 value of 0.86 µM on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells for 24 h compared to dexamethasone (IC50 = 0.62 µM) and low cytotoxicity against RAW 264.7 cells. Compound 4g significantly inhibited NO produced by LPS-induced RAW 264.7 cells. Further studies showed that compound 4g markedly inhibited the expression of pro-inflammatory factors, including inducible nitric oxide syn...
Source: Steroids - Category: Drugs & Pharmacology Source Type: research