Newboulasides A and B, two new caffeic acid glycosides from Newbouldia laevis with α-amylase inhibitory activity

Background: Neuraminidase (NA), a major glycoprotein found on the surface of the influenza virus, is an important target for the prophylaxis and treatment of influenza virus infections. Recently, several plant-derived polyphenols, especially caffeic acid analogs, have been reported to exert the inhibitory activity against NA. Objective: Herein, we aimed to investigate the anti-influenza NA activity of caffeic acid and its hydroxycinnamate analogues, rosmarinic acid and salvianolic acid A, in comparison to a known NA inhibitor, oseltamivir. Methods: In vitro MUNANA-based NA inhibitory assay was used to evaluate the inhibitory activity of the three interested hydroxycinnamic compounds towards the influenza NA enzyme. Subsequently, allatom molecular dynamics (MD) simulations and binding free energy calculations were employed to elucidate the structural insights into the protein-ligand complexations. Results: Rosmarinic acid showed the highest inhibitory activity against NA with the IC50 of 0.40 μM compared to caffeic acid (IC50 of 0.81 μM) and salvianolic acid A (IC50 of >1 μM). From 100-ns MD simulations, the binding affinity, hot-spot residues, and H-bond formations of rosmarinic acid/NA complex were higher than those of caffeic acid/NA model, in which their molecular complexations was driven mainly by electrostatic attractions and H-bond formations from several charged residues (R118, E119, D151, R152, E227, E277, and R371). Notably, the two hydroxyl groups on both phenyl and phenylacetic rings of rosmarinic acid play a crucial role in stabilizing NA through a strongly formed Hbond( s). Conclusion: Our findings shed light on the potentiality of rosmarinic acid as a lead compound for further development of a potential influenza NA inhibitor.

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Enzymatic transformation of caffeic acid with enhanced cyclooxygenase-2 inhibitory activity

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2011.12.072 ◽

2012 ◽

Vol 22 (2) ◽

pp. 793-796 ◽

Cited By ~ 15

Author(s):

Jong-Sup Bae ◽

Tae Hoon Kim

Keyword(s):

Caffeic Acid ◽

Inhibitory Activity ◽

Cyclooxygenase 2 ◽

Enzymatic Transformation

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New Hydroxycinnamic Acid Esters as Novel 5-Lipoxygenase Inhibitors That Affect Leukotriene Biosynthesis

Mediators of Inflammation ◽

10.1155/2017/6904634 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 10

Author(s):

Luc H. Boudreau ◽

Grégoire Lassalle-Claux ◽

Marc Cormier ◽

Sébastien Blanchard ◽

Marco S. Doucet ◽

...

Keyword(s):

Caffeic Acid ◽

Inhibitory Activity ◽

Inflammatory Diseases ◽

Caffeic Acid Phenethyl Ester ◽

Lipoxygenase Inhibitor ◽

Lipoxygenase Inhibitors ◽

Naturally Occurring ◽

Key Enzyme ◽

Hydroxycinnamic Acid Esters ◽

Acid Esters

Leukotrienes are inflammatory mediators that actively participate in the inflammatory response and host defense against pathogens. However, leukotrienes also participate in chronic inflammatory diseases. 5-lipoxygenase is a key enzyme in the biosynthesis of leukotrienes and is thus a validated therapeutic target. As of today, zileuton remains the only clinically approved 5-lipoxygenase inhibitor; however, its use has been limited due to severe side effects in some patients. Hence, the search for a better 5-lipoxygenase inhibitor continues. In this study, we investigated structural analogues of caffeic acid phenethyl ester, a naturally-occurring 5-lipoxygenase inhibitor, in an attempt to enhance the inhibitory activity against 5-lipoxygenase and determine structure-activity relationships. These compounds were investigated for their ability to attenuate the biosynthesis of leukotrienes. Compounds 13 and 19, phenpropyl and diphenylethyl esters, exhibited significantly enhanced inhibitory activity when compared to the reference molecules caffeic acid phenethyl ester and zileuton.

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Caffeic Acid Oligomers with Hyaluronidase Inhibitory Activity from Clinopodium gracile

Chemical and Pharmaceutical Bulletin ◽

10.1248/cpb.60.499 ◽

2012 ◽

Vol 60 (4) ◽

pp. 499-507 ◽

Cited By ~ 10

Author(s):

Hiroaki Aoshima ◽

Toshio Miyase ◽

Tsutomu Warashina

Keyword(s):

Caffeic Acid ◽

Inhibitory Activity

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Inhibitory effects of bioaccessible anthocyanins and procyanidins from apple, red grape, cinnamon on α-amylase, α-glucosidase and lipase

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000652 ◽

2020 ◽

pp. 1-9

Author(s):

Pınar Ercan ◽

Sedef Nehir El

Keyword(s):

Inhibitory Activity ◽

Digestive Enzymes ◽

Positive Control ◽

Anthocyanin Content ◽

Inhibitory Effects ◽

Total Anthocyanin ◽

Total Anthocyanin Content ◽

Before And After ◽

Red Grape

Abstract. The goals of this study were to determine and evaluate the bioaccessibility of total anthocyanin and procyanidin in apple (Amasya, Malus communis), red grape (Papazkarası, Vitis vinifera) and cinnamon (Cassia, Cinnamomum) using an in vitro static digestion system based on human gastrointestinal physiologically relevant conditions. Also, in vitro inhibitory effects of these foods on lipid (lipase) and carbohydrate digestive enzymes (α-amylase and α-glucosidase) were performed with before and after digested samples using acarbose and methylumbelliferyl oleate (4MUO) as the positive control. While the highest total anthocyanin content was found in red grape (164 ± 2.51 mg/100 g), the highest procyanidin content was found in cinnamon (6432 ± 177.31 mg/100 g) (p < 0.05). The anthocyanin bioaccessibilities were found as 10.2 ± 1%, 8.23 ± 0.64%, and 8.73 ± 0.70% in apple, red grape, and cinnamon, respectively. The procyanidin bioaccessibilities of apple, red grape, and cinnamon were found as 17.57 ± 0.71%, 14.08 ± 0.74% and 18.75 ± 1.49%, respectively. The analyzed apple, red grape and cinnamon showed the inhibitory activity against α-glucosidase (IC50 544 ± 21.94, 445 ± 15.67, 1592 ± 17.58 μg/mL, respectively), α-amylase (IC50 38.4 ± 7.26, 56.1 ± 3.60, 3.54 ± 0.86 μg/mL, respectively), and lipase (IC50 52.7 ± 2.05, 581 ± 54.14, 49.6 ± 2.72 μg/mL), respectively. According to our results apple, red grape and cinnamon have potential to inhibit of lipase, α-amylase and α-glucosidase digestive enzymes.

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