ABSTRACT
Phytochemical investigations of the twigs of Avicennia marina yielded three new abietane diterpenoids 11-hydroxy-8,11,13-abietatriene 12- O-beta-xylopyranoside ( 1), and a pair of inseparable epimers 6 Halpha-11,12,16-trihydroxy-6,7-secoabieta-8,11,13-triene-6,7-dial 11,6-hemiacetal ( 2) and 6 Hbeta-11,12,16-trihydroxy-6,7-secoabieta-8,11,13-triene-6,7-dial 11,6-hemiacetal ( 3), as well as the new lignan (7' S,8' R)-4,4',9'-trihydroxy-3,3',5,5'-tetramethoxy-7,8-dehydro-9-al-2,7'-cyclolignan ( 5), together with 6,11,12,16-tetrahydroxy-5,8,11,13-abitetetraen-7-one ( 4), lyoniresinol ( 6), lyoniresinol 9'- O-beta- D-glucopyranoside ( 7), and diacetylmartynoside ( 8). Structure elucidation of the new compounds was accomplished by analysis of their spectroscopic data. Compounds 2 - 4 showed moderate cytotoxic and antimicrobial activities.
Subject(s)
Abietanes/chemistry , Avicennia/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Molecular StructureABSTRACT
Piperine, a natural product containing a conjugated diene, was reacted with polymer-supported acyl- and arylnitroso dienophiles. The reactions with arylnitroso dienophiles were also carried out in solution. The oxazine rings formed by the corresponding hetero-Diels-Alder reactions were further transformed and novel acyclic as well as heterocyclic derivatives including pyrroles and quinoxalinones were prepared.
Subject(s)
Alkaloids/chemistry , Benzodioxoles/chemistry , Biological Products/chemistry , Nitroso Compounds/chemistry , Piperidines/chemistry , Polyunsaturated Alkamides/chemistryABSTRACT
Immobilized arylnitroso dienophiles were prepared and used in hetero Diels-Alder (HDA) reactions with a variety of dienes. Polymer-supported arylnitroso species were prepared on several linkers cleavable by different cleavage reagents and used for (i) optimization of reaction conditions for HDA reactions, (ii) evaluation of the reaction outcome with various dienes, (iii) comparison of relative reactivities of dienes, and (iv) assessment of the stability of HDA adducts toward cleavage conditions typically used in solid-phase preparation (TFA). The outcome of the HDA reactions has been evaluated for a set of 19 dienes, and the relative reactivities of dienes that yielded the expected HDA adducts were compared. Cleaved products were submitted to biological assays, and the results are reported.
Subject(s)
Combinatorial Chemistry Techniques/methods , Heterocyclic Compounds/chemical synthesis , Nitroso Compounds/chemical synthesis , Polymers/chemistry , Feasibility Studies , Heterocyclic Compounds/chemistry , Molecular Structure , Nitroso Compounds/chemistryABSTRACT
Polymer-supported dihydro[1,2]oxazine derivatives were prepared by acyl- and arylnitroso hetero-Diels-Alder reactions and exposed to strong (trifluoroacetic) acid during cleavage from resin-bound linkers. Cycloadducts prepared from cyclic dienes containing electron-donating substituents at the C6 oxazine carbon promoted formation of carbocations by cleavage of the C-O bond. The carbocations were quenched by nucleophilic reagents including triethylsilane, water, and alcohols and provided access to novel derivatives of N-alkyl hydroxamates. Products were submitted to biological assays, and the results are reported.
Subject(s)
Combinatorial Chemistry Techniques/methods , Heterocyclic Compounds/chemical synthesis , Nitroso Compounds/chemical synthesis , Oxazines/chemical synthesis , Polymers/chemistry , Trifluoroacetic Acid/chemistry , Carbon/chemistry , Cyclization , Heterocyclic Compounds/chemistry , Molecular Structure , Nitroso Compounds/chemistry , Oxazines/chemistry , Oxygen/chemistry , StereoisomerismABSTRACT
Polymer-supported acylnitroso dienophiles were prepared and used in hetero Diels-Alder (HDA) reactions with a variety of dienes. The transient acylnitroso dienophiles were prepared in situ from immobilized hydroxamates, which were attached to solid supports via several linkers each cleavable by different cleavage reagents, and served for the synthesis of both N-unsubstituted and N-derivatized HDA adducts. Model compounds were used to (i) optimize reaction conditions for solid-supported HDA reactions, (ii) evaluate the outcome of the reactions with various dienes, (iii) compare relative reactivities of dienes, and (iv) assess the stability of HDA adducts toward cleavage conditions typically used in solid-phase syntheses. Cleaved products were submitted to biological assays, and the results are reported. The accompanying paper, focused on complementary arylnitroso HDA reactions, includes a comparison of both HDA reactions.
Subject(s)
Combinatorial Chemistry Techniques/methods , Heterocyclic Compounds/chemical synthesis , Nitroso Compounds/chemical synthesis , Polymers/chemistry , Acylation , Feasibility Studies , Heterocyclic Compounds/chemistry , Hydroxamic Acids/chemistry , Molecular Structure , Nitroso Compounds/chemistry , Oxazines/chemistry , Oxidation-ReductionABSTRACT
Sanionins A (1) and B (2) were isolated from the moss Sanionia georgico-uncinata, collected on the Antarctic Livingston Island. The compounds 1 and 2 were purified by solvent extraction, silica gel column chromatography, and preparative HPLC, consecutively. The structures of the both compounds were elucidated by 1D and 2D NMR experiments and mass spectrometric investigations. These compounds showed activity against important Gram-positive pathogens, such as mycobacteria, multiresistant staphylococci, and vancomycin resistant enterococci. This activity is combined with antiinflammatoric activity and low cytotoxicity.
Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/toxicity , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/toxicity , Bibenzyls/pharmacology , Bibenzyls/toxicity , Bryophyta/chemistry , Plants, Medicinal/chemistry , Animals , Antarctic Regions , Anti-Bacterial Agents/isolation & purification , Anti-Inflammatory Agents/isolation & purification , Bibenzyls/isolation & purification , Cell Proliferation/drug effects , Chromatography, Gel , Chromatography, High Pressure Liquid , Epithelial Cells/drug effects , Fibroblasts/drug effects , Gram-Positive Bacteria/drug effects , HeLa Cells , Humans , K562 Cells , L Cells , Leukemia, Erythroblastic, Acute/drug therapy , Mass Spectrometry , Mice , Microbial Sensitivity Tests , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Solubility , Solvents/chemistry , Spectrometry, Mass, Electrospray IonizationABSTRACT
Pseudomonas aeruginosa is an opportunistic human pathogen that can cause a wide range of clinical symptoms and infections that are frequent in immunocompromised patients. In this study, we show that P. aeruginosa evades human complement attack by binding the human plasma regulators Factor H and Factor H-related protein-1 (FHR-1) to its surface. Factor H binds to intact bacteria via two sites that are located within short consensus repeat (SCR) domains 6-7 and 19-20, and FHR-1 binds within SCR domain 3-5. A P. aeruginosa Factor H binding protein was isolated using a Factor H affinity matrix, and was identified by mass spectrometry as the elongation factor Tuf. Factor H uses the same domains for binding to recombinant Tuf and to intact bacteria. Factor H bound to recombinant Tuf displayed cofactor activity for degradation of C3b. Similarly Factor H bound to intact P. aeruginosa showed complement regulatory activity and mediated C3b degradation. This acquired complement control was rather effective and acted in concert with endogenous proteases. Immunolocalization identified Tuf as a surface protein of P. aeruginosa. Tuf also bound plasminogen, and Tuf-bound plasminogen was converted by urokinase plasminogen activator to active plasmin. Thus, at the bacterial surface Tuf acts as a virulence factor and binds the human complement regulator Factor H and plasminogen. Acquisition of host effector proteins to the surface of the pathogen allows complement control and may facilitate tissue invasion.
Subject(s)
Bacterial Proteins/immunology , Carrier Proteins/immunology , Complement Factor H/immunology , Peptide Elongation Factor Tu/immunology , Pseudomonas aeruginosa/pathogenicity , Animals , Bacterial Proteins/analysis , Bacterial Proteins/isolation & purification , Blood Proteins/immunology , Carrier Proteins/analysis , Carrier Proteins/isolation & purification , Cell Line , Humans , Peptide Elongation Factor Tu/analysis , Peptide Elongation Factor Tu/isolation & purification , Plasminogen/immunology , Pseudomonas aeruginosa/immunology , Recombinant Proteins/immunology , VirulenceABSTRACT
In a continuing search for novel bioactive compounds from marine mangrove plants, seven new naphthoquinone derivatives were isolated from Avicennia marina, namely, avicennone A (1), avicennone B (2), avicennone C (3), avicennone D (4), avicenone E (5), avicennone F (6), and avicennone G (7), along with the known compounds avicequinone A (8), stenocarpoquinone B (9), avicequinone C (10), avicenol A (11), and avicenol C (12). The chemical structures of 1-7 were elucidated by spectroscopic methods. Compounds 8-10, and a mixture of 4 and 5, which all contain a 4,9-dione group, showed strong antiproliferative and moderate cytotoxic activities, as well as antibacterial effects.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Avicennia/chemistry , Drugs, Chinese Herbal/isolation & purification , Naphthoquinones/chemistry , Naphthoquinones/isolation & purification , Plants, Medicinal/chemistry , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Humans , Mice , Molecular Structure , Naphthoquinones/pharmacology , Plant Stems/chemistry , Structure-Activity RelationshipABSTRACT
The phytochemical investigation of the stem of Bruguiera gymnorrhiza yielded five new aromatic compounds (1-5), of which the bruguierols A - C (1-3) represent a new structural skeleton in natural product chemistry. All structures have been determined by NMR spectroscopic studies. Among them, 3 showed moderate activity against Gram-positive and Gram-negative bacteria including mycobacteria and resistant strains (MICs 12.5 microg/mL).
