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Atherosclerosis is an inflammatory disorder of the vasculature and one of the underlying causes of cardiovasculardiseases. Numerous preventative and therapeutic approaches are being explored to limit the morbidity and mortalityof this disease. Nevertheless, some of the treatments cost greatly and contributed to various side effects; for example,statin therapy is associated with substantial residual cardiovascular risk as well as issues such as tolerability and patientdependent efficacy. Currently, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor has been attractinginterests in the drug discovery of atherosclerosis treatment, but ezetimibe, a successful PCSK9 inhibitor, is an expensivemonoclonal antibody. Thus, exploring new PCSK9 inhibitors is crucial in overcoming this constraint. In the previouswork, aaptaminoids and methyl benzoate were isolated from marine sponges Aaptos aaptos and Acanthaster planci,respectively. These compounds enhance the transcription of the peroxisome proliferator-activated receptor gamma(PPARγ) in the luciferase assay. PPARγ agonist was hypothesized to inhibit the expression of the PCSK9 gene becausethe former is a transcription factor toward the latter. The synthesis of three aaptaminoids and 11 methyl benzoatederivative was carried out to address its potential as a PCSK9 inhibitor. The structure of the synthesized compound waselucidated using nuclear magnetic resonance spectral and electron impact mass spectral data. The PCSK9 inhibitoryactivities were determined by luciferase assay. Four aaptaminoids, such as aaptamine, N1,N4-bisbenzylaaptamine,N4-[(3,4,5-trimethoxy)benzyl]aaptamine, and N1-[(3,4,5-trimethoxy)benzyl]aaptamine, and one benzamide derivative,N-(2,3-dihydro-1H-inden-2-yl)-2-methoxybenzamide, were found to inhibit the expression of PCSK9 gene.
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Objective: To evaluate the immunosuppressive effect on human phagocytes and antibacterial activity of dihydromorin and norartocarpetin isolated from Artocarpus heterophyllus heartwoods. Methods: Dihydromorin and norartocarpetin were isolated from Artocarpus heterophyllus heartwoods. A modified Boyden chamber was used to determine the chemotactic activity of human phagocyte. The respiratory burst was evaluated by chemiluminescence assay. Myeloperoxidase (MPO) activity was quantified using a colorimetric assay. The broth microdilution method was performed to assess their antibacterial activity. Results: Dihydromorin exhibited potent inhibitory effect on the chemotactic activity of polymorphonuclear neutrophils (PMNs) with an IC50 value of 5.03 μg/mL. Dihydromorin also inhibited reactive oxygen species production of whole blood cells, PMNs, and monocytes with IC50 values of 7.88, 7.59 and 7.24 μg/mL, respectively. Interestingly, dihydromorin also strongly inhibited the MPO activity of PMNs with an IC50 value of 5.24 μg/mL, which was lower than indomethacin (24.6 μg/mL). Molecular docking of dihydromorin and crystal structure of MPO showed that dihydromorin had close interaction with key amino acid residues such as Arg239 and Gln91. Antibacterial activity assay showed that only dihydromorin had a strong effect against Streptococcus pyogenes with MIC and MBC values of 15.62 and 31.25 μg/mL, respectively. Conclusions: The results suggest that dihydromorin could be developed as an anti-inflammatory and antibacterial agent.
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Objective: To evaluate the immunosuppressive effect on human phagocytes and antibacterial activity of dihydromorin and norartocarpetin isolated from Artocarpus heterophyllus heartwoods. Methods: Dihydromorin and norartocarpetin were isolated from Artocarpus heterophyllus heartwoods. A modified Boyden chamber was used to determine the chemotactic activity of human phagocyte. The respiratory burst was evaluated by chemiluminescence assay. Myeloperoxidase (MPO) activity was quantified using a colorimetric assay. The broth microdilution method was performed to assess their antibacterial activity.Results: Dihydromorin exhibited potent inhibitory effect on the chemotactic activity of polymorphonuclear neutrophils (PMNs) with an IC50 value of 5.03 μg/mL. Dihydromorin also inhibited reactive oxygen species production of whole blood cells, PMNs, and monocytes with IC50 values of 7.88, 7.59 and 7.24 μg/mL, respectively. Interestingly, dihydromorin also strongly inhibited the MPO activity of PMNs with an IC50 value of 5.24 μg/mL, which was lower than indomethacin (24.6 μg/mL). Molecular docking of dihydromorin and crystal structure of MPO showed that dihydromorin had close interaction with key amino acid residues such as Arg239 and Gln91. Antibacterial activity assay showed that only dihydromorin had a strong effect against Streptococcus pyogenes with MIC and MBC values of 15.62 and 31.25 μg/mL, respectively. Conclusions: The results suggest that dihydromorin could be developed as an anti-inflammatory and antibacterial agent.
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@#Inhibition of xanthine oxidase (XO) activity is an effective therapeutic approach for the treatment of diseases such as goutand hyperuricemia. Additionally, the use of XO inhibitors can further be extended to injury treatments such as ischemicreperfusion in various organs such as heart, liver and kidney. In this study, 7 aurone compounds were synthesized andtested on XO and compared with the positive control allopurinol. Compound 5e was identified as the most potent compoundand was able to inhibit half of XO activity at 33.23 μM followed by compounds 5f and 5d at 210.22 μM and 302.0 μM,respectively. Finally, molecular docking study was conducted to understand the important binding interactions of theselected aurone with the active site of XO.