Aflaquinolones A–G: Secondary Metabolites from Marine and Fungicolous Isolates of <i>Aspergillus</i> spp.

Neff, Scott A.; Lee, Sang Un; Asami, Yukihiro; Ahn, Jong Seog; Oh, Hyuncheol; Baltrušaitis, Jonas; Gloer, James B.; Wicklow, Donald T.

doi:10.1021/np200958r

Cited by 58 publications

(90 citation statements)

References 30 publications

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“…(Dadaepo Beach, Busan, S. Korea); the same report also detailed the isolation of the related aaquinolones A and B from a terrestrial Aspergillus sp. 169 Investigation of Aspergillus sp. (sediment, South China Sea) resulted in the isolation of seven chlorinated anthraquinones 169-175.…”

Section: Marine-sourced Fungi (Excluding From Mangroves)mentioning

confidence: 99%

Marine natural products

et al. 2014

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This review covers the literature published in 2012 for marine natural products, with 1035 citations (673 for the period January to December 2012) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1241 for 2012), together with the relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.

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Section: Marine-sourced Fungi (Excluding From Mangroves)mentioning

confidence: 99%

Marine natural products

et al. 2014

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“…For example, aflaquinolones A-G ( Figure 4b), scopuquinolone B, aniduquinolones A-C, 6-deoxyaflaquinolone F, isoaflaquinolone E, 14-hydroxyaflaquinolone E, aspoquinolones A-D were also isolated from the various fungus belonging to the specie Aspergillus. These compounds have shown to have useful medicinal properties [46][47][48]. Moreover, some 1,4-disubstituted 1,2,3,4-tetrahydroquinoline derivatives ( Figure 4c) were tested against HIV and few N-substituted tetrahydroquinoline derivatives were found to inhibit the reverse transcriptase enzyme of HIV-1 virus [49][50][51][52].…”

Section: Introductionmentioning

confidence: 99%

“…(a) 5-heptyl-1,2,3,4-tetrahydroquinoline[44]. (b) Aflaquinolone A[46]. (c) 1,4-disubstituted 1,2,3,4-tetrahydroquinoline[50] (d) Tetrahydroquinoline chemical structure.…”

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confidence: 99%

Innovative Three-Step Microwave-Promoted Synthesis of N-Propargyltetrahydroquinoline and 1,2,3-Triazole Derivatives as a Potential Factor Xa (FXa) Inhibitors: Drug Design, Synthesis, and Biological Evaluation

et al. 2020

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The coagulation cascade is the process of the conversion of soluble fibrinogen to insoluble fibrin that terminates in production of a clot. Factor Xa (FXa) is a serine protease involved in the blood coagulation cascade. Moreover, FXa plays a vital role in the enzymatic sequence which ends with the thrombus production. Thrombosis is a common causal pathology for three widespread cardiovascular syndromes: acute coronary syndrome (ACS), venous thromboembolism (VTE), and strokes. In this research a series of N-propargyltetrahydroquinoline and 1,2,3-triazole derivatives as a potential factor Xa (FXa) inhibitor were designed, synthesized, and evaluated for their FXa inhibitor activity, cytotoxicity activity and coagulation parameters. Rational design for the desired novel molecules was performed through protein-ligand complexes selection and ligand clustering. The microwave-assisted synthetic strategy of selected compounds was carried out by using Ullmann-Goldberg, N-propargylation, Mannich addition, Friedel-Crafts, and 1,3-dipolar cycloaddition type reactions under microwave irradiation. The microwave methodology proved to be an efficient way to obtain all novel compounds in high yields (73–93%). Furthermore, a thermochemical analysis, optimization and reactivity indexes such as electronic chemical potential (µ), chemical hardness (η), and electrophilicity (ω) were performed to understand the relationship between the structure and the energetic behavior of all the series. Then, in vitro analysis showed that compounds 27, 29–31, and 34 exhibited inhibitory activity against FXa and the corresponding half maximal inhibitory concentration (IC50) values were calculated. Next, a cell viability assay in HEK293 and HepG2 cell lines, and coagulation parameters (anti FXa, Prothrombin time (PT), activated Partial Thromboplastin Time (aPTT)) of the most active novel molecules were performed to determine the corresponding cytotoxicity and possible action on clotting pathways. The obtained results suggest that compounds 27 and 29 inhibited FXa targeting through coagulation factors in the intrinsic and extrinsic pathways. However, compound 34 may target coagulation FXa mainly by the extrinsic and common pathway. Interestingly, the most active compounds in relation to the inhibition activity against FXa and coagulation parameters did not show toxicity at the performed coagulation assay concentrations. Finally, docking studies confirmed the preferential binding mode of N-propargyltetrahydroquinoline and 1,2,3-triazole derivatives inside the active site of FXa.

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“…The insertion was also performed with 4-bromo substituted imide 4c to access an unnatural quinolinone derivative with a handle for cross coupling chemistry as well as O-benzyl substituted imide 4d to access aflaquinolone F (11). 18 In all cases, benzophenones 5a-h were obtained as the major product along with unreacted imide 4a-d. With the benzophenones 5a-h in hand, we next investigated an intramolecular reaction 10 to forge the 3,4-dioxygenated quinoline-2-one core. Using an excess of potassium tert-butoxide in tetrahydrofuran at 0 °C, the quinolinones 6a-g were obtained as single diastereomers (Scheme 2).…”

Section: Scheme 1 Outline Of the Workmentioning

confidence: 88%

Synthesis of Quinolinone Alkaloids via Aryne Insertions into Unsymmetric Imides in Flow

et al. 2018

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A general strategy for the synthesis of 3,4-dioxygenated quinolin-2-one natural products is reported. The key step is a regioselective insertion of arynes into unsymmetric imides. When performed in continuous flow, the reaction proceeded within minutes. The resulting N-acylated 2-aminobenzophenones were transformed to (±)-peniprequinolone, (±)-aflaquinolones E and F, (±)-6-deoxyaflaquinolone E, (±)-quinolinones A and B, and (±)-aniduquinolone C in 1-3 steps. 4 d MeCN CsF 3.7:1 33 5 d,e MeCN KF 4.0:1 20 a Reaction conditions: 4a (0.26 mmol, 1 equiv.), 3a (0.39 mmol, 1.5 equiv.), Fsource (0.52 mmol, 2 equiv.), solvent (2.0 mL), 60 °C, 16 h; b ratios were determined by 1 H NMR integration; c isolated yield; d conducted at 80 °C for 4 h; e 18-crown-6 (1 equiv.) and 4 Å mol sieves were used as additives. ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website.

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Aflaquinolones A–G: Secondary Metabolites from Marine and Fungicolous Isolates of Aspergillus spp.

Cited by 58 publications

References 30 publications

Marine natural products

Marine natural products

Innovative Three-Step Microwave-Promoted Synthesis of N-Propargyltetrahydroquinoline and 1,2,3-Triazole Derivatives as a Potential Factor Xa (FXa) Inhibitors: Drug Design, Synthesis, and Biological Evaluation

Synthesis of Quinolinone Alkaloids via Aryne Insertions into Unsymmetric Imides in Flow

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