Isolation and In Silico SARS-CoV-2 Main Protease Inhibition Potential of Jusan Coumarin, a New Dicoumarin from Artemisia glauca.

A new dicoumarin, jusan coumarin, (1), has been isolated from Artemisia glauca aerial parts. The chemical structure of jusan coumarin was estimated, by 1D, 2D NMR as well as HR-Ms spectroscopic methods, to be 7-hydroxy-6-methoxy-3-[(2-oxo-2H-chromen-6-yl)oxy]-2H-chromen-2-one. As the first time to be introduced in nature, its potential against SARS-CoV-2 has been estimated using various in silico methods. Molecular similarity and fingerprints experiments have been utilized for 1 against nine co-crystallized ligands of COVID-19 vital proteins. The results declared a great similarity between Jusan Coumarin and X77, the ligand of COVID-19 main protease (PDB ID: 6W63), Mpro. To authenticate the obtained outputs, a DFT experiment was achieved to confirm the similarity of X77 and 1. Consequently, 1 was docked against Mpro. The results clarified that 1 bonded in a correct way inside Mpro active site, with a binding energy of -18.45 kcal/mol. Furthermore, the ADMET and toxicity profiles of 1 were evaluated and showed the safety of 1 and its likeness to be a drug. Finally, to confirm the binding and understand the thermodynamic characters between 1 and Mpro, several molecular dynamics (MD) simulations studies have been administered. Additionally, the known coumarin derivative, 7-isopentenyloxycoumarin (2), has been isolated as well as ß-sitosterol (3).

Jusanin, a New Flavonoid from Artemisia commutata with an In Silico Inhibitory Potential against the SARS-CoV-2 Main Protease.

A new flavonoid, Jusanin, (1) has been isolated from the aerial parts of Artemisia commutata. The chemical structure of Jusanin has been elucidated using 1D, 2D NMR, and HR-Ms spectroscopic methods to be 5,2',4'-trihydroxy-6,7,5'-trimethoxyflavone. Being new in nature, the inhibition potential of 1 has been estimated against SARS-CoV-2 using different in silico techniques. Firstly, molecular similarity and fingerprint studies have been conducted for Jusanin against co-crystallized ligands of eight different SARS-CoV-2 essential proteins. The studies indicated the similarity between 1 and X77, the co-crystallized ligand SARS-CoV-2 main protease (PDB ID: 6W63). To confirm the obtained results, a DFT study was carried out and indicated the similarity of (total energy, HOMO, LUMO, gap energy, and dipole moment) between 1 and X77. Accordingly, molecular docking studies of 1 against the target enzyme have been achieved and showed that 1 bonded correctly in the protein's active site with a binding energy of -19.54 Kcal/mol. Additionally, in silico ADMET in addition to the toxicity evaluation of Jusanin against seven models have been preceded and indicated the general safety and the likeness of Jusanin to be a drug. Finally, molecular dynamics simulation studies were applied to investigate the dynamic behavior of the Mpro-Jusanin complex and confirmed the correct binding at 100 ns. In addition to 1, three other metabolites have been isolated and identified to be сapillartemisin A (2), methyl-3-[S-hydroxyprenyl]-cumarate (3), and ß-sitosterol (4).

Isolation and In Silico Anti-SARS-CoV-2 Papain-Like Protease Potentialities of Two Rare 2-Phenoxychromone Derivatives from Artemisia spp.

Two rare 2-phenoxychromone derivatives, 6-demethoxy-4`-O-capillarsine (1) and tenuflorin C (2), were isolated from the areal parts of Artemisia commutata and A. glauca, respectively, for the first time. Being rare in nature, the inhibition potentialities of 1 and 2 against SARS-CoV-2 was investigated using multistage in silico techniques. At first, molecular similarity and fingerprint studies were conducted for 1 and 2 against co-crystallized ligands of eight different COVID-19 enzymes. The carried-out studies indicated the similarity of 1 and 2 with TTT, the co-crystallized ligand of COVID-19 Papain-Like Protease (PLP), (PDB ID: 3E9S). Therefore, molecular docking studies of 1 and 2 against the PLP were carried out and revealed correct binding inside the active site exhibiting binding energies of -18.86 and -18.37 Kcal/mol, respectively. Further, in silico ADMET in addition to toxicity evaluation of 1 and 2 against seven models indicated the general safety and the likeness of 1 and 2 to be drugs. Lastly, to authenticate the binding and to investigate the thermodynamic characters, molecular dynamics (MD) simulation studies were conducted on 1 and PLP.

New Flavonoids from Boldoa purpurascens Cav.

Phytochemical analysis of the leaves of BOLDOA PURPURASCENS Cav. led to isolation of four flavone glycosides, three of which are new compounds. Their structures have been determined by mass spectrometry and by 1 D and 2 D NMR analysis, i. e., 4',5-dihydroxy-6,7-methylenedioxyflavonol 3- O-alpha- L-rhamnopyranosyl-(1-->2)-beta- D-xylopyranoside ( 1), 4',5-dihydroxy-6,7-methylenedioxyflavonol 3- O-beta- D-xylopyranoside ( 2), and 4',5-dihydroxy-6,7-methylenedioxyflavonol 3- O-alpha- L-rhamnopyranosyl-(1-->2)-beta- D-glucopyranoside ( 3). The known compound was 4',5-dihydroxy-6,7-methylenedioxyflavonol 3- O-beta- D-glucopyranoside ( 4). The aglycone 4',5-dihydroxy-6,7-methylenedioxyflavonol is known as gomphrenol. Compounds 1 and 2 failed to show antifungal activity when tested against three different strains of fungi, i. e., FUSARIUM CULMORUM, BOTRYTIS CINEREA, and ASPERGILLUS FLAVUS.

Facile synthesis of novel indolo[3,2-b]carbazole derivatives and a chromogenic-sensing 5,12-dihydroindolo[3,2-b]carbazole.

Novel indolo[3,2-b]carbazole derivatives and a chromogenic-sensing 5,12-dihydroindolo[3,2-b]carbazole have been synthesized starting from tetra-tert-butylated 6,12-diaryl-5,11-dihydroindolo[3,2-b]carbazoles, which were prepared via an efficient tert-butylation of 6,12-diaryl-5,11-dihydroindolo[3,2-b]carbazoles.

Oxidative reactions of 6-pentyl indolo[3,2-b]carbazole: formation of novel C-C and C-N coupled dimers.

The oxidative coupling reactions of 6-pentyl-5,11-dihydroindolo[3,2-b]carbazole have been studied and as a result, a number of novel dimers of the indolo[3,2-b]carbazole derivative have been prepared, forming C-C coupled compound when treated with FeCl(3) x 6H(2)O or C-N coupled compounds and when oxidized with air or Pd(OAc)(2), respectively.

Identification of steviol glucuronide in human urine.

Stevioside (250 mg capsules) was given three times daily to 10 healthy subjects. Steviol glucuronide (steviol 19-O-beta-D-glucopyranosiduronic acid; MM, 494.58; melting point, 198-199 degrees C) was characterized in the 24 h urine as the only excretion product of oral stevioside by MS, NMR, IR, and UV spectroscopy. This is the first report on the unambiguous identification of steviol glucuronide in human urine.

Steviol quantification at the picomole level by high-performance liquid chromatography.

A simple and highly sensitive reversed-phase high-performance liquid chromatographic method (RP-HPLC) has been developed for the determination of steviol (SV) using dihydroisosteviol (DHISV) as an internal standard (IS). SV and DHISV were derivatized by reaction of the acids with 4-(bromomethyl)-7-methoxycoumarin in an aprotic solvent (DMF or acetone). The resulting ester derivatives were separated on an ODS column (250 x 4.6 mm i.d., 5 microm particle size) using fluorescence detection with excitation at 321 nm and emission at 391 nm. The mobile phase consisted of acetonitrile/water (80:20 v/v) with a flow rate of 1 mL min(-)(1). A linear relationship was observed for concentrations between 0.5 and 50 microg/mL of SV, and the detection limit was 100 pg. For application of this method to samples of beer fortified with stevioside, a simple procedure for extraction of the beer with diethyl ether and derivatization in DMF was applied. Whereas beer samples spiked with SV gave a linear response over the range 0.1-15 microg/mL beer, no SV could be detected in beer samples enriched in stevioside that had been stored for over 3 years. The application of the method to plant samples involved preparation of an acid fraction containing the SV analyte, derivatization, and sample cleanup using small silica columns and thin-layer chromatography. A sensitive determination of 594 ng of steviol present in 100 mg of dry plant material was performed with high precision and accuracy.

Reactions of 5-mercaptoazoles and pyridine-2-thiones with acetylenic esters. Selectivity of the formation of novel fused thiazin-4-ones and thiazolidin-4-ones.

A systematic study of the reactions of dimethyl acetylenedicarboxylate (DMAD) and methyl propynoate with 5-mercaptoazoles and pyridine-2-thiones has been carried out and as a result, a number of novel imidazo[1,5-b]thiazin-4-ones 6a,b, pyrazolo[1,5-b] thiazin-4-ones 15a-f, imidazo[1,5-b]thiazol-4-ones 7a,b and thiazolo[3,2-a]pyridines 21a-c have been prepared. The influence of the size of the ring of the starting "cyclic" thioamides on the size of the fused ring in the reaction products has been established. The preferred formation of a six-membered thiazine ring took place in the reactions of 5-mercaptoazoles. In contrast, the five membered thiazolidine ring is formed in reactions of pyridine-2-thiones. In both cases the product is a five-membered ring fused to a six-membered heterocycle.