Department of Therapeutic Chemistry, National Research Centre, Dokki, Cairo 12622, Egypt.
Department of Therapeutic Chemistry, National Research Centre, Dokki, Cairo 12622, Egypt.
Bioorg Chem. 2021 Jun;111:104827. doi: 10.1016/j.bioorg.2021.104827. Epub 2021 Mar 17.
A new set of derivatives bearing pyrazole-methylenehydrazono-thiazolidinone scaffold 4-23 was designed, synthesized and confirmed by different spectroscopic means and elemental analyses. In-vivo anti-inflammatory and ulcerogenic evaluation was performed for all the newly synthesized derivatives using indomethacin, celecoxib and diclofenac as standard drugs. The compounds 5, 10, 15, 17, 21, 22 appeared to be the most promising candidates producing rapid onset and long duration of anti-inflammatory activity as well as promising GIT safety profile. Furthermore, analgesic evaluation revealed that the compounds 5, 10, 15 and 22 produced potent and long acting analgesia accompanied with significant inhibition of the inflammatory cytokine TNF-α level in comparison with the standard drugs. Molecular docking study of the latter derivatives was also carried out to rationalize their binding affinities and their modes of interactions with the active site of TNF-α.
设计、合成并通过不同的光谱手段和元素分析确认了一组新的含有吡唑亚甲基腙噻唑烷酮支架的衍生物 4-23。使用吲哚美辛、塞来昔布和双氯芬酸作为标准药物，对所有新合成的衍生物进行了体内抗炎和致溃疡评价。化合物 5、10、15、17、21、22 似乎是最有前途的候选药物，它们具有快速起效和长时间抗炎活性以及有希望的胃肠道安全性。此外，镇痛评价表明，与标准药物相比，化合物 5、10、15 和 22 产生了强大且长效的镇痛作用，并显著抑制了炎症细胞因子 TNF-α 的水平。还对这些衍生物进行了分子对接研究，以合理化它们与 TNF-α 活性位点的结合亲和力和相互作用模式。
