Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Hamdard University, New Delhi, India.
Arch Pharm (Weinheim). 2018 Apr;351(3-4):e1700304. doi: 10.1002/ardp.201700304. Epub 2018 Mar 8.
Recent studies have demonstrated that inhibition of p38α MAP kinase could effectively inhibit pro-inflammatory cytokines including TNF-α and interleukins. Thus, inhibition of this enzyme can prove greatly beneficial in the therapy of chronic inflammatory diseases. A new series of N-[3-(substituted-4H-1,2,4-triazol-4-yl)]-benzo[d]thiazol-2-amines (4a-n) were synthesized and subjected to in vitro evaluation for anti-inflammatory activity (BSA anti-denaturation assay) and p38α MAPK inhibition. Among the compounds selected for in vivo screening of anti-inflammatory activity (4b, 4c, 4f, 4g, 4j, 4m, and 4n), compound 4f was found to be the most active with an in vivo anti-inflammatory efficacy of 85.31% when compared to diclofenac sodium (83.68%). It was also found to have a low ulcerogenic risk and a protective effect on lipid peroxidation. The p38α MAP kinase inhibition of this compound (IC = 0.036 ± 0.12 μM) was also found to be superior to the standard SB203580 (IC = 0.043 ± 0.27 μM). Furthermore, the in silico binding mode of the compound on docking against p38α MAP kinase exemplified stronger interactions than those of SB203580.
最近的研究表明，抑制 p38α MAP 激酶可以有效抑制包括 TNF-α 和白细胞介素在内的促炎细胞因子。因此，抑制这种酶在慢性炎症性疾病的治疗中可能非常有益。我们合成了一系列新的 N-[3-(取代-4H-1,2,4-三唑-4-基)]-苯并[d]噻唑-2-胺（4a-n），并对其进行了抗炎活性（BSA 抗变性测定）和 p38α MAPK 抑制作用的体外评价。在所选择的用于抗炎活性体内筛选的化合物（4b、4c、4f、4g、4j、4m 和 4n）中，化合物 4f 的抗炎活性最强，与双氯芬酸钠（83.68%）相比，体内抗炎效果为 85.31%。此外，它还具有较低的致溃疡风险和对脂质过氧化的保护作用。该化合物对 p38α MAP 激酶的抑制作用（IC = 0.036 ± 0.12 μM）也优于标准 SB203580（IC = 0.043 ± 0.27 μM）。此外，化合物在对接 p38α MAP 激酶时的计算机模拟结合模式例证了比 SB203580 更强的相互作用。
