Pancreatic Lipase (PL) is a key enzyme responsible for the digestion of 50%–70% of dietary triglycerides, hence its inhibition is considered as a viable approach for the management of obesity. A series of indole-TZD hybrid analogues were synthesized, characterized and evaluated for their PL inhibitory activity. Knoevenagel condensation of various substituted indole-3-carboxaldehyde with substituted thiazolidinediones resulted in the formation of titled analogues. Analogues 6d and 6e exerted potent PL inhibitory activity (IC₅₀-6.19 and 8.96 µM, respectively). Further, these analogues exerted a competitive mode of PL inhibition. Moreover, molecular modelling studies were in agreement with the in vitro results (Pearson's r = .8682, p < .05). The fluorescence spectroscopic analysis further supported the strong binding affinity of these analogues with PL. A molecular dynamics study (20 ns) indicated that these analogues were stable in a dynamic environment. Thus, the present study highlighted the potential role of indole-thiazolidinedione hybrid analogues as potential PL inhibitors and further optimization might result in the development of new PL inhibitory lead candidates.

中文翻译：

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作为潜在胰脂肪酶抑制剂的 N-取代吲哚-噻唑烷二酮类似物的设计、合成和生物学评价

胰脂肪酶 (PL) 是负责消化 50%–70% 膳食甘油三酯的关键酶，因此其抑制被认为是控制肥胖的可行方法。合成、表征和评估了一系列吲哚-TZD 杂化类似物的 PL 抑制活性。各种取代的吲哚-3-甲醛与取代的噻唑烷二酮的 Knoevenagel 缩合导致形成标题类似物。类似物6d和6e发挥有效的 PL 抑制活性（IC ₅₀ -6.19 和 8.96 µM，分别）。此外，这些类似物发挥了竞争性的 PL 抑制模式。此外，分子模型研究与体外结果一致（Pearson's r = .8682，p  < .05）。荧光光谱分析进一步支持这些类似物与 PL 的强结合亲和力。分子动力学研究 (20 ns) 表明这些类似物在动态环境中是稳定的。因此，本研究强调了吲哚-噻唑烷二酮杂化类似物作为潜在 PL 抑制剂的潜在作用，进一步优化可能会导致开发新的 PL 抑制先导候选物。