Human neutrophil elastase inhibitory dihydrobenzoxanthones and alkylated flavones from the Artocarpus elasticus root barks

Abstract

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).

Analogues of Dihydroflavonol and Flavone as Protein Tyrosine Phosphatase 1B Inhibitors from the Leaves of Artocarpus elasticus

“…Their structures (as shown in Figure 1) were elucidated by their spectroscopic data (Figures S1−S49 and Table S1) and compared with those of previous reports. The isolates (3−13) were identified as artoscortonol 19 (3), glepidotin B 20 (4), yukovanol 21 (5), dihydrokaempferol 22 (6), atalantoflavone 23 (7), apigenin 24 (8), 2′-hydroxyatalantoflavone 25 (9), norartocarpetin 10 (10), engeletin 26 (11), isoengeletin 26 (12), and apigenin-7-O-β-D-glucopyranoside 27 (13). Compounds 1 and 2 were found to be new dihydroflavonols.…”

“…This study explored PTP1B inhibitory metabolites from the leaves of Artocarpus elasticus. The responsible metabolites for PTP1B (IC 50 = 0.17−35.41 μM) were identified as eight dihydroflavonols (1−6, 11, 12) and five flavones (7)(8)(9)(10)13). Inhibitory potency and behavior were significantly affected by chemical skeleton and functionality.…”

Anticancer mechanism of artonin E and related prenylated flavonoids from the medicinal plant Artocarpus elasticus

“…Other artoindonesianins have been found in A. elasticus, such as artoindonesianin P which was found to inhibit the enzyme -glucosidase (IC50 = 25.4 M) but with a reduced efficacy compared to Art-E and artobiloxanthone (IC50 = 16.2 and 8.6 M, respectively) (Jenis et al 2019). Recently, artoindonesianins P and W were isolated from A. elasticus and found to inhibit human neutrophil elastase (IC50 = 28.7 and 11.2 M, respectively) whereas artobiloxanthone was slightly more active (IC50 = 9.8 M) (Ban et al 2020).…”

Antioxidant, Tyrosinase, α-Glucosidase, and Elastase Enzyme Inhibition Activities of Optimized Unripe Ajwa Date Pulp (Phoenix dactylifera) Extracts by Response Surface Methodology

“…NE can destroy elements of the coagulation and fibrinolytic pathways, as well as activate matrix metalloproteinases and deactivate their inhibitors. Following this, an excess of HNE may cause a number of pathological illnesses and tissue damage, including rheumatoid arthritis, psoriasis, cystic fibrosis, chronic obstructive lung disease, acute respiratory distress syndrome, pulmonary fibrosis, and pulmonary fibrosis [ 14 , 15 , 16 , 17 ]. The ability of the serine protease inhibitors to control the proteolytic activities of the serine proteases makes them vital for restoring the balance between the protease and anti-protease systems, limiting excessive elastin proteolysis, and lowering neutrophil accumulation at inflammatory areas [ 13 , 15 ].…”

“…The ability of the serine protease inhibitors to control the proteolytic activities of the serine proteases makes them vital for restoring the balance between the protease and anti-protease systems, limiting excessive elastin proteolysis, and lowering neutrophil accumulation at inflammatory areas [ 13 , 15 ]. Natural compounds such as polyphenolic compounds (ugonins Q: IC 50 = 0.49 μM, quercetin-3-O-glucoside; IC 50 = 0.35 μM, 6,8-diprenylorobol; IC 50 = 1.3 μM, and amentoflavone; IC 50 = 1.27 μM) are primarily found in herbal plants and have been shown to affect elastase release [ 12 , 14 ].…”