新合成的二苯甲酮噻唑杂环具有体内外抗炎活性

IF 3.2 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Luiz Paulo Melchior de Oliveira Leão, Albert Katchborian Neto, Karen de Jesus Nicácio, Stefânia Neiva Lavorato, Fernanda Brito Leite, Karina Camargo Teixeira, Michael Murgu, Ana Cláudia Chagas de Paula, Marisi Gomes Soares, Daniela Aparecida Chagas-Paula, Danielle Ferreira Dias
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引用次数: 0

摘要

我们合成了具有不同取代基的新型二苯甲酮-噻唑混合物,并利用体内外人体全血试验对其抗炎活性进行了评估。所有杂交化合物(3c 和 5a-h)都通过抑制前列腺素 E2(PGE2)的释放而显示出显著的抗炎活性。此外,5c(82.8% 的 PGE2 抑制率)、5e(83.1% 的 PGE2 抑制率)和 5h(82.1% 的 PGE2 抑制率)的抗炎活性与参考药物相当。分子对接显示,这些药物与环氧化酶 2(COX-2)和微粒体前列腺素 E 合酶-1(mPGES-1)酶的活性位点有潜在的更优结合。这项研究首次证明,二苯甲酮-噻唑混合物除了具有良好的体内外抗炎性能外,还能与具有吸引力的抗炎药物新靶点--mPGES-1对接。因此,这些新型杂交化合物是很有前景的抗炎先导化合物,并突出了在设计强效 PGE2 抑制剂时选择最佳取代基的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Novel Synthesized Benzophenone Thiazole Hybrids Exhibited Ex Vivo and In Silico Anti-Inflammatory Activity

Novel benzophenone–thiazole hybrids with different substituents were synthesized and evaluated for anti-inflammatory activity using an ex vivo human whole-blood assay. All hybrids (3c and 5a–h) showed significant anti-inflammatory activity via prostaglandin E2 (PGE2) release inhibition. Moreover, 5c (82.8% of PGE2 inhibition), 5e (83.1% of PGE2 inhibition), and 5h (82.1% of PGE2 inhibition) were comparable to the reference drugs. Molecular docking revealed potential preferable binding to the active sites of cyclooxygenase 2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) enzymes. This study provides the first evidence that benzophenone–thiazole hybrids may also dock in mPGES-1, a new attractive anti-inflammatory drug target, besides providing promising ex vivo anti-inflammatory activity. Thus, the novel hybrids are promising anti-inflammatory lead compounds and highlight the significance of optimal substituent selection in the design of potent PGE2 inhibitors.

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来源期刊
Chemical Biology & Drug Design
Chemical Biology & Drug Design 医学-生化与分子生物学
CiteScore
5.10
自引率
3.30%
发文量
164
审稿时长
4.4 months
期刊介绍: Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.
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