Neutrophil elastases are deposited in azurophilic granules interspace of neutrophils and tightly associated with inflammatory ailments. The root barks of Artocarpus elasticus had a strong inhibitory potential against human neutrophil elastase (HNE). The responsible components for HNE inhibition were confirmed as alkylated flavones (2–4, IC50 = 14.8 ~ 18.1 μM) and dihydrobenzoxanthones (5–8, IC50 = 9.8 ~ 28.7 μM). Alkyl groups on flavone were found to be crucial functionalities for HNE inhibition. For instance, alkylated flavone 2 (IC50 = 14.8 μM) was 20-fold potent than mother compound norartocarpetin (1, IC50 > 300 μM). The kinetic analysis showed that alkylated flavones (2–4) were noncompetitive inhibition, while dihydrobenzoxanthones (5–8) were a mixed type I (KI < KIS) inhibitors, which usually binds with free enzyme better than to complex of enzyme–substrate. Inhibitors and HNE enzyme binding affinities were examined by fluorescence quenching effect. In the result, the binding affinity constants (KSV) had a significant correlation with inhibitory potencies (IC50).

中文翻译：

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面包果皮根皮中人嗜中性白细胞弹性蛋白酶抑制性二氢苯并氧杂蒽酮和烷基化黄酮

中性粒细胞弹性蛋白酶沉积在嗜中性粒细胞的嗜氮颗粒间隙中，并与炎性疾病紧密相关。面包果皮的根皮对人中性粒细胞弹性蛋白酶（HNE）具有很强的抑制潜力。确认对HNE抑制作用的主要成分为烷基化黄酮（2-4，IC50 = 14.8〜18.1μM）和二氢苯并氧杂蒽酮（5-8，IC50 = 9.8〜28.7μM）。黄酮上的烷基被发现是抑制HNE的关键功能。例如，烷基化的黄酮2（IC50 = 14.8μM）的效力是母体化合物Norartocarpetin（1，IC50> 300μM）的20倍。动力学分析表明，烷基化黄酮（2-4）是非竞争性抑制剂，而二氢苯并氧杂蒽酮（5-8）是I型混合抑制剂（KI <KIS），通常与游离酶结合比与酶-底物复合物结合更好。通过荧光猝灭作用检查抑制剂和HNE酶的结合亲和力。结果，结合亲和力常数（KSV）与抑制能力（IC50）有显着相关性。