Coronavirus Disease 2019 (COVID-19) is an infectious illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), originally identified in Wuhan, China (December 2019) and has since expanded into a pandemic. Here, we investigate metabolites present in several common spices as possible inhibitors of COVID-19. Specifically, 32 compounds isolated from 14 cooking seasonings were examined as inhibitors for SARS-CoV-2 main protease (M pro ), which is required for viral multiplication. Using a drug discovery approach to identify possible antiviral leads, in silico molecular docking studies were performed. Docking calculations revealed a high potency of salvianolic acid A and curcumin as M pro inhibitors with binding energies of −9.7 and −9.2 kcal/mol, respectively. Binding mode analysis demonstrated the ability of salvianolic acid A and curcumin to form nine and six hydrogen bonds, respectively with amino acids proximal to M pro 's active site. Stabilities and binding affinities of the two identified natural spices were calculated over 40 ns molecular dynamics simulations and compared to an antiviral protease inhibitor (lopinavir). Molecular mechanics-generalized Born surface area energy calculations revealed greater salvianolic acid A affinity for the enzyme over curcumin and lopinavir with energies of −44.8, −34.2 and −34.8 kcal/mol, respectively. Using a STRING database, protein-protein interactions were identified for salvianolic acid A included the biochemical signaling genes ACE, MAPK14 and ESR1; and for curcumin, EGFR and TNF. This study establishes salvianolic acid A as an in silico natural product inhibitor against the SARS-CoV-2 main protease and provides a promising inhibitor lead for in vitro enzyme testing.
<p><strong>Objective:</strong><strong> </strong>To evaluate the <em>in vitro</em> cytotoxicity, antioxidant activities and structure-activity relationship of secondary metabolites isolated from <em>Pulicaria undulata</em>.</p><p><strong>Methods: </strong>The methylene chloride-methanol (1:1) extract of the air-dried aerial parts of <em>Pulicaria undulata</em> was fractionated and separated to obtain the isolated compounds by different chromatographic techniques. Structures of the isolated compounds were determined on the basis of the extensive spectroscopic analysis, including 1D and 2D NMR and compared with the literature data. The crude extract and the isolated compounds were evaluated for <em>in vitro</em> antioxidant activity using the 2,2 diphenyl dipicryl hydrazine (DPPH) method and cytotoxic assay using human breast cancer (MCF-7) and hepatoma (Hep G2) cell line.</p><p><strong>Results: </strong>Nine secondary metabolites were isolated from <em>Pulicaria undulata</em> in this study. Of which two terpenoidal compounds; 8-epi-ivalbin and 11β, 13-dihydro-4H-xanthalongin 4-<em>O</em>-β-D-glucopyranoside firstly isolated from the genus <em>pulicaria</em> and three flavonoids; eupatolitin, 6-methoxykaempferol, and patulitrin firstly isolated from <em>P. undulata</em>. 6-methoxykaempferol (IC<sub>50</sub> 2.3 µg/ml) showed the most potent antioxidant activity. The highest cytotoxic effect against MCF-7 and Hep G2 cells was obtained with eupatolitin (IC<sub>50</sub> 27.6 and 23.5 µg/ml) respectively. The structure-activity relationship was also examined and the findings presented here showed that 3, 5, 7, 4' and 3, 5, 4', 5'-hydroxy flavonoids were potent antioxidant and has cytotoxic activity.</p><p><strong>Conclusion: </strong><em>Pulicaria undulata</em> is a promising medicinal plant, and our study tends to support the therapeutic value of this plant as antioxidant drug and in the treatment of cancer.</p>
Centaurothamnus maximus (family Asteraceae), is a leafy shrub indigenous to the southwestern Arabian Peninsula. With a paucity of phytochemical data on this species, we set out to chemically characterize the plant. From the aerial parts, two newly identified guaianolides were isolated: 3β-hydroxy-4α(acetoxy)-4β(hydroxymethyl)-8α-(4-hydroxy methacrylate)-1αH,5αH, 6αH-gual-10(14),11(13)-dien-6,12-olide (1) and 15-descarboxy picrolide A (2). Seven previously reported compounds were also isolated: 3β, 4α, 8α-trihydroxy-4-(hydroxymethyl)-lαH, 5αH, 6βH, 7αH-guai-10(14),11(13)-dien-6,12-olide (3), chlorohyssopifolin B (4), cynaropikrin (5), hydroxyjanerin (6), chlorojanerin (7), isorhamnetin (8), and quercetagetin-3,6-dimethyl ether-4’-O-β-d-pyranoglucoside (9). Chemical structures were elucidated using spectroscopic techniques, including High Resolution Fast Atom Bombardment Mass Spectrometry (HR-FAB-MS), 1D NMR; 1H, 13C NMR, Distortionless Enhancement by Polarization Transfer (DEPT), and 2D NMR (1H-1H COSY, HMQC, HMBC) analyses. In addition, a biosynthetic pathway for compounds 1–9 is proposed. The chemotaxonomic significance of the reported sesquiterpenoids and flavonoids considering reports from other Centaurea species is examined.
The aerial parts of Centaureaa egyptiaca afforded 10 secondary metabolites including four sesquiterpene lactones; chlorohyssopifolin A (centaurepensin) (1), rediolpidetriol (2), linichlorinA (3), and sinaicin (4), one monoterpene; loliolid (5), one phenolic: tyrosol (6), three lignans; arctigenin (7), matairesinol (8), and pinoresinol (9), and one steroid; ergosta‐5,22‐dien‐3‐ol (10). The cluster analysis of 32 Centaurea species revealed that C. aegyptiaca is closely related to C. repens and C. solstitialise. The isolated compounds (1–10) were screened against CCRF‐CEM‐leukemia, MDA‐MB‐231‐pcDNA3 breast cancer, and HCT116 (p53+/+) colon carcinoma cell lines. Compounds1 and 2 were the most potent compounds against both leukemia and breast carcinoma cell lines.
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