Two independent mol-ecules (A and B) comprise the asymmetric unit of the title compound, C21H18O4. There are significant conformational differences between the mol-ecules relating in particular to the relative orientation of the 3-oxo-2-(phenyl-methyl-idene)but-oxy substituent with respect to the superimposable chromen-2-one residues. To a first approximation, the substituents are mirror images; both are approximately perpendicular to the chromen-2-one fused ring system with dihedral angles of 88.50 (7) (A) and 81.96 (7)° (B). Another difference between the independent mol-ecules is noted in the dihedral angles between the adjacent phenyl and but-3-en-2-one groups of 8.72 (12) (A) and 27.70 (10)° (B). The conformation about the ethene bond in both mol-ecules is E. The crystal packing features C-H⋯O, C-H⋯π(ar-yl) and π-π [Cg⋯Cg = 3.6657 (8) and 3.7778 (8) Å] stacking inter-actions, which generate a three-dimensional network.
The title compound, C(19)H(16)O, crystallizes with two molecules of opposite chirality in the asymmetric unit. In both molecules, the naphthalene and cyclopentanone moieties are individually planar. The two cyclopentane rings adopt envelope conformations, while the cyclohexane ring adopts a boat conformation.
Coumarins have received a considerable attention in the last three decades as a lead structures for the discovery of orally bioavailable non-peptidic antiviral agents. A lot of structurally diverse coumarins analogues were found to display remarkable array of affinity with the different molecular targets for antiviral agents and slight modifications around the central motif result in pronounced changes in its antiviral spectrum. This manuscript thoroughly reviews the design, discovery and structure-activity relationship studies of the coumarin analogues as antiviral agents focusing mainly on lead optimization and its development into clinical candidates.
In the title compound, C(26)H(22)O(4), the pyranone ring adopts a twisted boat conformation, while the cyclohexane ring is close to an envelope conformation. The dihedral angle between the mean planes of the coumarin and naphthalene systems is 78.8(1) degree. The attached phenyl ring is in an equatorial position with respect to the cyclohexane ring.
A new coumarin, 8,4''-dihydroxy-3'',4''-dihydrocapnolactone-2',3'-diol (1) and two known triterpenes, 5(6)-gluten-3-one (2) and 5(6)-gluten-3alpha-ol (3) were isolated from the leaves of Micromelum minutum (Rutaceae) collected from Sepilok, Sabah, Malaysia and their structures were characterized by spectroscopic methods.
New derivatives of 7-hydroxy-4-methylcoumarin were synthesized using a chemical method and a microwave-assisted method to compare the feasibility, reaction times, and yields of the product. The newly synthesized coumarins were characterized by different spectroscopic techniques (FT-IR and NMR) and micro-elemental analysis (CHNS). In vitro antioxidant activities of these compounds were evaluated against hydrogen peroxide and were compared with standard natural antioxidant, vitamin C. Our results reveal that these compounds exhibit excellent radical scavenging activities.
In a continuation of our study of the Rutaceae, detailed chemical investigation on Micromelum minutum (Rutaceae) collected from Sepilok, Sabah, Malaysia gave four new coumarins. The structures of the coumarins have been fully characterised by spectroscopic methods as 3",4"-dihydrocapnolactone 1, 2',3'-epoxyisocapnolactone 2, 8-hydroxyisocapnolactone-2',3'-diol 3 and 8-hydroxy-3",4"-dihydrocapnolactone-2',3'-diol 4.
The major enzyme responsible for the hydrolytic breakdown of the neurotransmitter acetylcholine (ACh) is acetylcholinesterase (AChE). Acetylcholinesterase inhibitors (AChEIs) are the most prescribed class of medications for the treatment of Alzheimer's disease (AD) and dementia. The limitations of available therapy, like side effects, drug tolerance, and inefficacy in halting disease progression, drive the need for better, more efficacious, and safer drugs. In this study, a series of fourteen novel chalcone-coumarin derivatives (8a-n) were designed, synthesized and characterized by spectral techniques like FT-IR, NMR, and HR-MS. Subsequently, the synthesized compounds were tested for their ability to inhibit acetylcholinesterase (AChE) activity by Ellman's method. All tested compounds showed AChE inhibition with IC50 value ranging from 0.201 ± 0.008 to 1.047 ± 0.043 μM. Hybrid 8d having chloro substitution on ring-B of the chalcone scaffold showed relatively better potency, with IC50 value of 0.201 ± 0.008 μM compared to other members of the series. The reference drug, galantamine, exhibited an IC50 at 1.142 ± 0.027 μM. Computational studies revealed that designed compounds bind to the peripheral anionic site (PAS), the catalytic active site (CAS), and the mid-gorge site of AChE. Putative binding modes, ligand-enzyme interactions, and stability of the best active compound are studied using molecular docking, followed by molecular dynamics (MD) simulations. The cytotoxicity of the synthesised derivatives was determined using the MTT test at three concentrations (100 g/mL, 500 g/mL, and 1 mg/mL). None of the chemicals had a significant effect on the body at the highest dose of 1 mg/mL.Communicated by Ramaswamy H. Sarma.
Newly synthesized coumarins 4-((5-mercapto-4-phenyl-4H-1,2,4-triazol-3-yl)-methoxy)-2H-chromen-2-one and 4-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)-methoxy)-2H-chromen-2-one were tested against selected types of fungi and showed significant activities. DFT calculations of the synthesized coumarins were performed using molecular structures with optimized geometries. Molecular orbital calculations provide a detailed description of the orbitals, including spatial characteristics, nodal patterns, and the contributions of individual atoms.
Species from the Genus Calophyllum are rich source for bioactive phenolic compounds such as coumarins and xanthones. Phytochemical study carried out on the plant, Calophyllum macrocarpum has led to the isolation of three known prenylated xanthones, ananixanthone (1), trapezifolixanthone (2) and 8-deoxygartanin (3) with two common triterpenoids, stigmasterol (4), and friedelin (5). The structures of these compounds were identified and determined using spectroscopic techniques such as NMR and MS. The cytotoxic activities of compounds 1 and 2 as well as the extracts were tested against HeLa Chang liver and HEK-293 cell lines. Compound 1 exhibited appreciable cytotoxicity with the IC50 value of 11.08 ± 3.09 µM against HeLa Chang liver cell line and moderate cytotoxicity against HEK-293 cell line while compound 2 showed limited toxicity against these two cell lines.
In our effort directed toward the discovery of new anti-diabetic agent for the treatment of diabetes, a library of biscoumarin derivative 1-18 was synthesized and evaluated for α-glucosidase inhibitory potential. All eighteen (18) compounds displayed assorted α-glucosidase activity with IC50 values 16.5-385.9 μM, if compared with the standard acarbose (IC50 = 906 ± 6.387 μM). In addition, molecular docking studies were carried out to explore the binding interactions of biscoumarin derivatives with the enzyme. This study has identified a new class of potent α-glucosidase inhibitors.
A significant acetylcholinesterase (AChE) inhibitory activity was observed for the hexane extract from the bark of Mesua elegans (Clusiaceae). Thus, the hexane extract was subjected to chemical investigation, which led to the isolation of nine 4-phenylcoumarins, in which three are new; mesuagenin A (1), mesuagenin C (3), mesuagenin D (4) and one new natural product; mesuagenin B (2). The structures of the isolated compounds were characterized by spectroscopic data interpretation, especially 1D and 2D NMR. Four compounds showed significant AChE inhibitory activity, with mesuagenin B (2) being the most potent (IC(50)=0.7μM).
From the aerial parts of Atriplex littoralis, three new flavonoid glycosides named atriplexins I-III (1-3), a known flavonoid glycoside, spinacetin 3-O-β-d-glucopyranoside (4), arbutin (5), and 4-hydroxybenzyl-β-d-glucopyranoside (6) were isolated. Their structures were elucidated on the basis of detailed spectroscopic analysis, including 1D and 2D NMR (COSY, NOESY, TOCSY, HSQC, HMBC) and HRESITOF MS data. The compounds were tested for in vitro protective effects on chromosome aberrations in peripheral human lymphocytes using a cytochalasin-B-blocked micronucleus (MN) assay in a concentration range of 0.8-7.4 μM of final culture solution. Chromosomal damage was induced by 2 Gy of γ-radiation on binucleated human lymphocytes, and the effects of the compounds were tested 2 to 19 h after irradiation. The frequency of micronuclei (MNi) was scored in binucleated cells, and the nuclear proliferation index was calculated. The highest prevention of in vitro biochemical and cytogenetic damage of human lymphocytes induced by γ-radiation was exhibited by 3 (reduction of MN frequency by 31%), followed by 4 and 6.
Our recent studies on the stem bark of Calophyllum mucigerum (Guttiferae) have yielded a new coumarin mucigerin, a prenylated xanthone cudraxanthone C and the common steroidal triterpenes friedelin and stigmasterol. Structural elucidations of these compounds were achieved using 1H NMR, 13C NMR, DEPT, COSY, HETCOR and HMBC experiments while MS gave the molecular masses. Cytotoxic assays using CEM-SS cell line (T-lymphoblastic leukemia) on the crude extracts of the stem bark indicated some activity. The crude extracts were also found to be moderately toxic against the larvae of Aedes aegypti. This article reports the isolation and identification of mucigerin as well as bioassay data.
The coumarin ring system in the title asymmetric alkyne, C18H12O2, is approximately planar (r.m.s. deviation of the 11 non-H atoms = 0.048 Å), and is inclined with respect to the methyl-benzene ring, forming a dihedral angle of 33.68 (4)°. In the crystal, supra-molecular zigzag chains along the c-axis direction are formed via weak C-H⋯O hydrogen bonds, and these are connected into double layers via weak C-H⋯π inter-actions; these stack along the a axis.
The extract of Cinnamomum microphyllum showed strong antioxidant activity when it was tested against auto-oxidation of linoleic acid, superoxide, and DPPH radical scavenging activity. Further detailed investigations of the plant constituents and bioactivity studies led to the isolation and identification of known compounds consisting of three lignans, a coumarin, an ester and β-sitosterol. The structures of the compounds were determined using detailed spectroscopic analysis. The lignans were found to possess a significant antioxidant activity when tested against the three assay systems.
Thymidine phosphorylase (TP) over expression plays role in several pathological conditions, such as rheumatoid arthritis, chronic inflammatory diseases, psoriasis, and tumor angiogenesis. The inhibitor of this enzyme plays an important role in preventing the serious threat due to over expression of TP. In this regard, a series of seventeenanalogs of 3-formylcoumarin (1-17) were synthesized, characterized by 1HNMR and EI-MS and screened for thymidine phosphorylaseinhibitory activity. All analogs showed a variable degree of thymidine phosphorylase inhibition with IC50 values ranging between 0.90 ± 0.01 and 53.50 ± 1.20 μM when compared with the standard inhibitor 7-Deazaxanthine having IC50 value 38.68 ± 1.12 μM. Among the series, fifteenanalogs such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 16 and 17 showed excellent inhibition which is many folds better than the standard 7-Deazaxanthine whiletwo analogs 13 and 14 showed good inhibition. The structure activity relationship (SAR) was mainly based upon by bring about difference of substituents on phenyl ring. Molecular docking study was carried out to understand the binding interaction of the most active analogs.
Syntheses of coumarins, which are a structurally interesting antioxidant activity, was done in this article. The modification of 7-hydroxycoumarin by different reaction steps was done to yield target compounds. Molecular structures were characterized by different spectroscopical techniques (Fourier transformation infrared and nuclear magnetic resonance). Antioxidant activities were performed by using various in vitro spectrophometric assays against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and hydrogen peroxide (H2O2). All compounds exhibited high efficiency as antioxidants compared to ascorbic acid. The highest efficiency scavenging activity was found for compound 3 (91.0 ± 5.0), followed by compounds 2 and 4 (88.0 ± 2.00; and 87.0 ± 3.00). Ascorbic acid C was used as a standard drug with a percentage inhibition of 91.00 ± 1.5. The mechanism of the synthesized compounds as antioxidants was also studied. Hartree-Fock-based quantum chemical studies have been carried out with the basis set to 3-21G, in order to obtain information about the three-dimensional (3D) geometries, electronic structure, molecular modeling, and electronic levels, namely HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital), to understand the antioxidant activity for the synthesized compounds.
3-Thiazolylcoumarin derivatives 1-14 were synthesized via one-pot two step reactions, and screened for in vitro α-glucosidase inhibitory activity. All compounds showed inhibitory activity in the range of IC50 = 0.12 ± 0.01-16.20 ± 0.23 μM as compared to standard acarbose (IC50 = 38.25 ± 0.12 μM), and also found to be nontoxic. Molecular docking study was carried out in order to establish the structure-activity relationship (SAR) which demonstrated that electron rich centers at one and electron withdrawing centers at the other end of the molecules showed strong inhibitory activity. All the synthesized compounds were characterized by spectroscopic techniques such as EI-MS, HREI-MS, (1)H NMR and (13)C NMR. CHN analysis was also performed.
The anticorrosion ability of a synthesized coumarin, namely 2-(coumarin-4-yloxy)acetohydrazide (EFCI), for mild steel (MS) in 1 M hydrochloric acid solution has been studied using a weight loss method. The effect of temperature on the corrosion rate was investigated, and some thermodynamic parameters were calculated. The results indicated that inhibition efficiencies were enhanced with an increase in concentration of inhibitor and decreased with a rise in temperature. The IE value reaches 94.7% at the highest used concentration of the new eco-friendly inhibitor. The adsorption of inhibitor on MS surface was found to obey a Langmuir adsorption isotherm. Scanning electron microscopy (SEM) was performed on inhibited and uninhibited mild steel samples to characterize the surface. The Density Function theory (DFT) was employed for quantum-chemical calculations such as EHOMO (highest occupied molecular orbital energy), ELUMO (lowest unoccupied molecular orbital energy) and μ (dipole moment), and the obtained results were found to be consistent with the experimental findings. The synthesized inhibitor was characterized by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopic studies.