Novel Heterocyclic Hybrids Based on 2-Pyrazoline: Synthesis and Assessment of Anti-Inflammatory and Analgesic Activities

Abstract

A series of new 2-pyrazoline analogues were synthesized. The structures of the synthesized compounds were elucidated by the analytical and spectroscopic data. Some selected compounds were screened for the anti-inflammatory activity by using animal model of carrageenan-induced paw edema in mice. Additionally, the analgesic and acute toxicity of these compounds were evaluated and exhibited reasonable results. The anti-oxidant and anti-inflammatory effects of these compounds were established by measuring the contents of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), and tumor necrosis factor alpha (TNF-α) in the edema paw tissue. All chemicals and reagents used in current study were of analytical grade. Melting points were determined using APP. Digital ST 15 melting point apparatus and are uncorrected. FT-IR spectra were recorded on a Pye-Unicam SP3-100 spectrophotometer in KBr pellet. All 1H and 13C NMR spectra were recorded on AVANCE-III (400 MHz) High Performance FT-NMR Spectrometer Brucker (Switzerland) and some 1H NMR spectra were recorded on Varian EM-360L NMR Spectrophotometer (60 MHz) (USA) in CDCl3 or DMSO-d6 as solvent. Chemical shifts are reported in δ units and the coupling constants (J) are reported in hertz. C, H, N and S analyses were performed with a Vario EL C, H, N, S Analyzer. Carrageenan (product number C1013) was obtained from Sigma-Aldrich (USA). The structures of the compounds were confirmed by IR, 1H NMR, 13C NMR, and elemental analyses. The results of pharmacological activity revealed that compounds 5, 6, 7, and 15 could be recognized as potential multi-potent anti-inflammatory. A simple and suitable method for the synthesis of new pharmacophore was reported. We have designed nineteen heterocycles related to pyrazoline ring, and evaluated eleven of them for their antiinflammatory, analgesic and acute toxicity activities. Compounds 5, 6, 7, and 15 proved to be the interesting compounds, they have high anti-inflammatory activity. However, all the selected compounds show remarkable analgesic activity.