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1.
Microb Cell Fact ; 19(1): 3, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906943

RESUMO

Using an established CRISPR-Cas mediated genome editing technique for streptomycetes, we explored the combinatorial biosynthesis potential of the auroramycin biosynthetic gene cluster in Streptomyces roseosporous. Auroramycin is a potent anti-MRSA polyene macrolactam. In addition, auroramycin has antifungal activities, which is unique among structurally similar polyene macrolactams, such as incednine and silvalactam. In this work, we employed different engineering strategies to target glycosylation and acylation biosynthetic machineries within its recently elucidated biosynthetic pathway. Auroramycin analogs with variations in C-, N- methylation, hydroxylation and extender units incorporation were produced and characterized. By comparing the bioactivity profiles of five of these analogs, we determined that unique disaccharide motif of auroramycin is essential for its antimicrobial bioactivity. We further demonstrated that C-methylation of the 3, 5-epi-lemonose unit, which is unique among structurally similar polyene macrolactams, is key to its antifungal activity.


Assuntos
Antibacterianos/biossíntese , Antifúngicos/química , Vias Biossintéticas/genética , Engenharia Metabólica/métodos , Streptomyces/genética , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Sistemas CRISPR-Cas , Edição de Genes/métodos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Polienos/química , Streptomyces/metabolismo
2.
Angew Chem Int Ed Engl ; 59(16): 6540-6545, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-31944523

RESUMO

The cross-conjugated vinylogous [4+2] anionic annulation has been newly developed, the cascade process of which has a high preference for regiochemical control and chemoselectivity, giving rise to exclusively Michael-type adducts in moderate to high yields (up to 94 %, 35 examples). By making use of this approach as a key operation, the first total synthesis of natural antibiotic ABX, in racemic form, has been successfully achieved in a concise 7-step sequence with an overall yield of about 20 %.

3.
J Med Chem ; 63(4): 1642-1659, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-31961685

RESUMO

Indoleamine 2,3-dioxygenase (IDO1) inhibitors are speculated to be useful in cancer immunotherapy, but a phase III clinical trial of the most advanced IDO1 inhibitor, epacadostat, did not meet its primary end point and was abandoned. In previous work, we identified the novel IDO1 inhibitor N-(4-chlorophenyl)-2-((5-phenylthiazolo[2,3-c][1,2,4]triazol-3-yl)thio)acetamide 1 through high-throughput screening (HTS). Herein, we report a structure-activity relationship (SAR) study of this compound, which resulted in the potent IDO1 inhibitor 1-(4-cyanophenyl)-3-(3-(cyclopropylethynyl)imidazo[2,1-b]thiazol-5-yl)thiourea 47 (hIDO IC50 = 16.4 nM). X-ray cocrystal structural analysis revealed that the basis for this high potency is a unique sulfur-aromatic interaction network formed by the thiourea moiety of 47 with F163 and F226. This finding is expected to inspire new approaches toward the discovery of potent IDO1 inhibitors in the future.

4.
J Med Chem ; 62(13): 6047-6062, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31181158

RESUMO

We report that compound 13, a novel phosphatidylserine-targeting zinc(II) dipicolylamine drug conjugate, readily triggers a positive feedback therapeutic loop through the in situ generation of phosphatidylserine in the tumor microenvironment. Linker modifications, pharmacokinetics profiling, in vivo antitumor studies, and micro-Western array of treated-tumor tissues were employed to show that this class of conjugates induced regeneration of apoptotic signals, which facilitated subsequent recruitment of the circulating conjugates through the zinc(II) dipicolylamine-phosphatidylserine association and resulted in compounding antitumor efficacy. Compared to the marketed compound 17, compound 13 not only induced regressions in colorectal and pancreatic tumor models, it also exhibited at least 5-fold enhancement in antitumor efficacy with only 40% of the drug employed during treatment, culminating in a >12.5-fold increase in therapeutic potential. Our study discloses a chemically distinct apoptosis-targeting theranostic, with built-in complementary functional moieties between the targeting module and the drug mechanism to expand the arsenal of antitumor therapy.

5.
Cell Chem Biol ; 26(5): 662-673.e7, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-30827936

RESUMO

The G protein-coupled receptor (GPCR) CXCR4 is a co-receptor for HIV and is involved in cancers and autoimmune diseases. We characterized five purine or quinazoline core polyamine pharmacophores used for targeting CXCR4 dysregulation in diseases. All were neutral antagonists for wild-type CXCR4 and two were biased antagonists with effects on ß-arrestin-2 only at high concentrations. These compounds displayed various activities for a constitutively active mutant (CAM). We use the IT1t-CXCR4 crystal structure and molecular dynamics (MD) simulations to develop two hypotheses for the activation of the N1193.35A CAM. The N1193.35A mutation facilitates increased coupling of TM helices III and VI. IT1t deactivates the CAM by disrupting the coupling between TM helices III and VI, mediated primarily by residue F872.53. Mutants of F872.53 in N1193.35A CXCR4 precluded constitutive signaling and prevented inverse agonism. This work characterizes CXCR4 ligands and provides a mechanism for N1193.35A constitutive activation.

6.
Bioorg Med Chem ; 27(1): 216-223, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30528163

RESUMO

The [18F] isotope-labelled CB1 inverse agonist 3 was elaborated and synthesized for positron emission tomography scanning studies. After immediate purification and calibration with its unlabeled counterpart, compound 3 was intravenously injected in mice and revealed that its distribution percentage in brain over 90-min scans among five region of interests, including brain, liver, heart, thigh muscle and kidney was lower than 1%, thus providing direct evidence to justify itself as a peripherally restricted CB1 antagonist.


Assuntos
Agonistas de Receptores de Canabinoides/farmacologia , Pirazóis/farmacologia , Receptor CB1 de Canabinoide/agonistas , Sulfonamidas/farmacologia , Tiofenos/farmacologia , Animais , Agonistas de Receptores de Canabinoides/síntese química , Agonistas de Receptores de Canabinoides/química , Agonistas de Receptores de Canabinoides/farmacocinética , Agonismo Inverso de Drogas , Radioisótopos de Flúor , Marcação por Isótopo , Masculino , Camundongos Endogâmicos C57BL , Tomografia por Emissão de Pósitrons/métodos , Pirazóis/síntese química , Pirazóis/química , Pirazóis/farmacocinética , Receptor CB1 de Canabinoide/antagonistas & inibidores , Sulfonamidas/síntese química , Sulfonamidas/química , Sulfonamidas/farmacocinética , Tiofenos/química , Tiofenos/farmacocinética , Distribuição Tecidual
7.
J Org Chem ; 83(23): 14688-14697, 2018 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-30277073

RESUMO

Making use of temperature-controlled thiation as a key operation, a simple route to 2-aminothiophenes or thieno[2,3- c]isothiazoles has been newly developed wherein the 2-aminothiophene nucleus was formed through an initial formation of thioamide followed by a 5-exo-dig addition to the tethered alkyne; however, under harsher thermal conditions, excess sulfur-transferring reagents enabled further oxidative thiation to generate the corresponding thieno[2,3- c]isothiazoles.

8.
J Food Drug Anal ; 26(3): 1015-1023, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29976394

RESUMO

Curcumin (Cur), a polyphenolic compound extracted from spice and common food colourant turmeric, contains versatile bio-activities. Monoacetylcurcumin (MAC), a structural analogue of Cur, differs from Cur by acetyl modification, but retains enone groups. Comparative analysis revealed MAC effectively inhibited influenza virus infection (IAV) to a similar extent as, if not superior to, curcumin. Both compounds mildly reduced viral NA activity. Surprisingly, unlike Cur, the MAC inhibition of IAV did not occur through the blocking of HA activity. However, MAC strongly dampened Akt phosphorylation, the prerequisite signalling for efficient IAV propagation. A much stronger inhibition effect on IAV infection was observed when MAC treatment was in combination with Cur. Collectively, MAC demonstrated clear antiviral activity, and likely inhibited IAV via multiple mechanisms that were not identical to Cur. Importantly, Cur and MAC in combination synergistically inhibited IAV infection.


Assuntos
Antivirais/farmacologia , Curcumina/análogos & derivados , Curcumina/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Influenza Humana/virologia , Animais , Antivirais/química , Curcumina/química , Cães , Sinergismo Farmacológico , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/fisiologia , Influenza Humana/tratamento farmacológico , Influenza Humana/genética , Influenza Humana/metabolismo , Células Madin Darby de Rim Canino , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Replicação Viral/efeitos dos fármacos
9.
J Org Chem ; 83(12): 6508-6523, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29785848

RESUMO

Making use of a reductive olefin coupling reaction and Michael-Dieckmann condensation as two key operations, we have completed a concise total synthesis of tetarimycin A, (±)-naphthacemycin A9, and (±)-fasamycin A in a highly convergent and practical protocol. Synthetic procedures thus developed have also been applied to provide related analogues for structure-activity relationship studies, thereby coming to the conclusion that the free hydroxyl group at C-10 is essential for exerting inhibitory activities against a panel of Gram-positive bacteria, including drug-resistant strains VRE and MRSA.


Assuntos
Compostos de Bifenilo/síntese química , Compostos de Bifenilo/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Naftacenos/síntese química , Naftacenos/farmacologia , Hidrocarbonetos Policíclicos Aromáticos/síntese química , Hidrocarbonetos Policíclicos Aromáticos/farmacologia , Compostos Policíclicos/síntese química , Compostos Policíclicos/farmacologia , Relação Estrutura-Atividade
10.
Chembiochem ; 2018 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-29799651

RESUMO

Silent biosynthetic gene clusters represent a potentially rich source of new bioactive compounds. We report the discovery, characterization, and biosynthesis of a novel doubly glycosylated 24-membered polyene macrolactam from a silent biosynthetic gene cluster in Streptomyces roseosporus by using the CRISPR-Cas9 gene cluster activation strategy. Structural characterization of this polyketide, named auroramycin, revealed a rare isobutyrylmalonyl extender unit and a unique pair of amino sugars. Relative and absolute stereochemistry were determined by using a combination of spectroscopic analyses, chemical derivatization, and computational analysis. The activated gene cluster for auroramycin production was also verified by transcriptional analyses and gene deletions. Finally, auroramycin exhibited potent anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity towards clinical drug-resistant isolates.

11.
J Med Chem ; 61(3): 818-833, 2018 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-29314840

RESUMO

The function of the CXCR4/CXCL12 axis accounts for many disease indications, including tissue/nerve regeneration, cancer metastasis, and inflammation. Blocking CXCR4 signaling with its antagonists may lead to moving out CXCR4+ cell types from bone marrow to peripheral circulation. We have discovered a novel series of pyrimidine-based CXCR4 antagonists, a representative (i.e., 16) of which was tolerated at a higher dose and showed better HSC-mobilizing ability at the maximal response dose relative to the approved drug 1 (AMD3100), and thus considered a potential drug candidate for PBSCT indication. Docking compound 16 into the X-ray crystal structure of CXCR4 receptor revealed that it adopted a spider-like conformation striding over both major and minor subpockets. This putative binding mode provides a new insight into CXCR4 receptor-ligand interactions for further structural modifications.


Assuntos
Transplante de Células-Tronco de Sangue Periférico , Receptores CXCR4/metabolismo , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Animais , Células HEK293 , Compostos Heterocíclicos/metabolismo , Compostos Heterocíclicos/farmacologia , Humanos , Concentração Inibidora 50 , Masculino , Camundongos , Simulação de Acoplamento Molecular , Conformação Proteica , Receptores CXCR4/química
12.
Med Res Rev ; 38(4): 1188-1234, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-28768055

RESUMO

CXCR4 antagonists (e.g., PlerixaforTM ) have been successfully validated as stem cell mobilizers for peripheral blood stem cell transplantation. Applications of the CXCR4 antagonists have heralded the era of cell-based therapy and opened a potential therapeutic horizon for many unmet medical needs such as kidney injury, ischemic stroke, cancer, and myocardial infarction. In this review, we first introduce the central role of CXCR4 in diverse cellular signaling pathways and discuss its involvement in several disease progressions. We then highlight the molecular design and optimization strategies for targeting CXCR4 from a large number of case studies, concluding that polyamines are the preferred CXCR4-binding ligands compared to other structural options, presumably by mimicking the highly positively charged natural ligand CXCL12. These results could be further justified with computer-aided docking into the CXCR4 crystal structure wherein both major and minor subpockets of the binding cavity are considered functionally important. Finally, from the clinical point of view, CXCR4 antagonists could mobilize hematopoietic stem/progenitor cells with long-term repopulating capacity to the peripheral blood, promising to replace surgically obtained bone marrow cells as a preferred source for stem cell transplantation.


Assuntos
Quimiocina CXCL12/química , Infecções por HIV/tratamento farmacológico , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Receptores CXCR4/antagonistas & inibidores , Animais , Doenças Autoimunes/tratamento farmacológico , Ensaios Clínicos como Assunto , Cristalografia por Raios X , Humanos , Imunoterapia , Ligantes , Isquemia Miocárdica/tratamento farmacológico , Metástase Neoplásica , Neutrófilos/citologia , Peptídeos/química , Regeneração , Transdução de Sinais , Transplante de Células-Tronco
13.
Bioconjug Chem ; 28(7): 1878-1892, 2017 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-28581724

RESUMO

A series of zinc(II) dipicolylamine (ZnDPA)-based drug conjugates have been synthesized to probe the potential of phosphatidylserine (PS) as a new antigen for small molecule drug conjugate (SMDC) development. Using in vitro cytotoxicity and plasma stability studies, PS-binding assay, in vivo pharmacokinetic studies, and maximum tolerated dose profiles, we provided a roadmap and the key parameters required for the development of the ZnDPA based drug conjugate. In particular, conjugate 24 induced tumor regression in the COLO 205 xenograft model and exhibited a more potent antitumor effect with a 70% reduction of cytotoxic payload compared to that of the marketed irinotecan when dosed at the same regimen. In addition to the validation of PS as an effective pharmacodelivery target for SMDC, our work also provided the foundation that, if applicable, a variety of therapeutic agents could be conjugated in the same manner to treat other PS-associated diseases.


Assuntos
Antineoplásicos/farmacocinética , Imunoconjugados/uso terapêutico , Terapia de Alvo Molecular/métodos , Compostos Organometálicos/imunologia , Fosfatidilserinas/imunologia , Ácidos Picolínicos/imunologia , Animais , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Humanos , Imunoconjugados/química , Imunoconjugados/farmacocinética , Compostos Organometálicos/síntese química , Compostos Organometálicos/farmacologia , Fosfatidilserinas/metabolismo , Ácidos Picolínicos/síntese química , Ácidos Picolínicos/farmacologia , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Cell Transplant ; 26(4): 571-583, 2017 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-27938478

RESUMO

C-X-C chemokine receptor type 4 (CXCR4) is a receptor for a pleiotropic chemokine CXCL12. Previous studies have shown that the acute administration of the CXCR4 antagonist AMD3100 reduced neuroinflammation in stroke brain and mobilized bone marrow hematopoietic stem cells (HSCs). The purpose of this study was to characterize the neuroprotective and neurotrophic effect of a novel CXCR4 antagonist CX549. We demonstrated that CX549 had a higher affinity for CXCR4 and was more potent than AMD3100 to inhibit CXCL12-mediated chemotaxis in culture. CX549 effectively reduced the activation of microglia and improved neuronal survival after injury in neuron/microglia cocultures. Early poststroke treatment with CX549 significantly improved behavioral function, reduced brain infarction, and suppressed the expression of inflammatory markers. Compared to AMD3100, CX549 has a higher affinity for CXCR4, is more efficient to mobilize HSCs for transplantation, and induces behavioral improvement. Our data support that CX549 is a potent anti-inflammatory agent, is neuroprotective against ischemic brain injury, and may have clinical implications for the treatment of stroke.


Assuntos
Encéfalo/patologia , Neuroproteção , Fármacos Neuroprotetores/uso terapêutico , Quinazolinas/uso terapêutico , Receptores CXCR4/antagonistas & inibidores , Acidente Vascular Cerebral/tratamento farmacológico , Triazóis/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Infarto Encefálico/complicações , Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/patologia , Quimiotaxia/efeitos dos fármacos , Células HEK293 , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Compostos Heterocíclicos/farmacologia , Humanos , Interleucina-6/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/patologia , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Quinazolinas/farmacologia , Ratos Sprague-Dawley , Receptores CXCR4/metabolismo , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologia , Triazóis/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
15.
ACS Med Chem Lett ; 7(12): 1191-1196, 2016 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-27994762

RESUMO

Series of N-substituted carbazole analogues bearing an indole ring were synthesized as anti-methicillin-resistant Staphylococcus aureus (MRSA) agents from a molecular hybridization approach. The representative compound 19 showed an MIC = 1 µg/mL against a panel of MRSA clinical isolates as it possessed comparable in vitro activities to that of vancomycin. Moreover, compound 19 also exhibited MIC = 1 µg/mL activities against a recent identified Z172 MRSA strain (vancomycin-intermediate and daptomycin-nonsusceptible phenotype) and the vancomycin-resistant Enterococcus faecalis (VRE) strain. In a mouse model with lethal infection of MRSA (4N216), a 75% survival rate was observed after a single dose of compound 19 was intravenously administered at 20 mg/kg. In light of their equipotent activities against different MRSA isolates and VRE strain, the data underscore the importance of designed hybrid series for the development of new N-substituted carbazoles as potential anti-MRSA agents.

16.
J Org Chem ; 81(22): 10759-10768, 2016 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-27750001

RESUMO

A new N-hydroxyphthalimide (NHPI)/Co(II)-catalyzed protocol, mechanistically involving a sequence of α-hydrogen abstraction, 5-exo-dig cyclization, oxygen capture, hydrogen transfer, and 1,4-dehydration, has been developed to facilitate aerobic oxidation of aryl-, silyl-, and alkyl-capped alkynyl α-cyano alkanone systems to the corresponding highly functionalized products in an effective manner, thus turning this novel chain reaction, originally occurring spontaneously in low yields, into a practical methodology.

17.
J Med Chem ; 59(1): 282-93, 2016 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-26642377

RESUMO

Indoleamine 2,3-dioxygenase 1 (IDO1), promoting immune escape of tumors, is a therapeutic target for the cancer immunotherapy. A number of IDO1 inhibitors have been identified, but only limited structural biology studies of IDO1 inhibitors are available to provide insights on the binding mechanism of IDO1. In this study, we present the structure of IDO1 in complex with 24, a NLG919 analogue with potent activity. The complex structure revealed the imidazole nitrogen atom of 24 to coordinate with the heme iron, and the imidazoleisoindole core situated in pocket A with the 1-cyclohexylethanol moiety extended to pocket B to interact with the surrounding residues. Most interestingly, 24 formed an extensive hydrogen bond network with IDO1, which is a distinct feature of IDO1/24 complex structure and is not observed in the other IDO1 complex structures. Further structure-activity relationship, UV spectra, and structural biology studies of several analogues of 24 demonstrated that extensive hydrophobic interactions and the unique hydrogen bonding network contribute to the great potency of imidazoleisoindole derivatives. These results are expected to facilitate the structure-based drug design of new IDO inhibitors.


Assuntos
Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Imidazóis/síntese química , Imidazóis/farmacologia , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Cristalografia por Raios X , Desenho de Fármacos , Humanos , Ligação de Hidrogênio , Modelos Moleculares , Relação Estrutura-Atividade
18.
Org Biomol Chem ; 14(1): 220-8, 2016 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-26552357

RESUMO

Tandem reactions use consecutive reaction steps to efficiently synthesize compounds of high molecular complexity. This paper presents a tandem Pd-catalyzed Heck and alkoxycarbonylation reaction for the stereoselective synthesis of (E)-oxindolylidene acetates. The mechanism underlying the Pd-catalyzed tandem reaction involves the syn-carbopalladation of ynamides followed by alkoxycarbonylation with CO and alcohol. This method makes it possible to obtain the desired (E)-configuration of oxindolylidene acetates exclusively. We evaluated the scope of the reaction by applying optimal reaction conditions to the facile synthesis of a library of (E)-oxindolylidene acetates. The resulting (E)-oxindolylidene acetates exhibited potent anticancer activities against a variety of human cancer cell lines. The anticancer activities of some (E)-oxindolylidene acetates were even superior to those of known CDK inhibitors indirubin-3'-oxime and roscovitine.


Assuntos
Antineoplásicos/farmacologia , Quinases Ciclina-Dependentes/antagonistas & inibidores , Indóis/farmacologia , Compostos Organometálicos/química , Paládio/química , Inibidores de Proteínas Quinases/farmacologia , Álcoois/química , Amidas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Monóxido de Carbono/química , Catálise , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indóis/síntese química , Indóis/química , Estrutura Molecular , Oxindois , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade
19.
Org Lett ; 17(17): 4248-51, 2015 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-26273719

RESUMO

Making use of the Hauser-Kraus annulation as a key step, the first total synthesis of tetarimycin A has been accomplished in a highly convergent and operationally simple manner. Preliminary SAR not only validated that tetarimycin A exhibited potent activity against MRSA and VRE at a low MIC value but also identified that the hydroxyl group at C-10 was essential for antibacterial activities.


Assuntos
Antibacterianos/síntese química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Compostos Policíclicos/síntese química , Compostos Policíclicos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Policíclicos/química , Relação Estrutura-Atividade
20.
J Org Chem ; 80(13): 6708-14, 2015 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-26047161

RESUMO

Making use of a tandem free radical cyclization process mediated by Mn(OAc)3 as a key operation, the total synthesis of retrojusticidin B, justicidin E, and helioxanthin has been concisely achieved in four or five steps in an overall yield of 45, 33 and 44%, respectively, from a common starting material 5.


Assuntos
Dioxolanos/síntese química , Lignanas/síntese química , Naftalenos/síntese química , Catálise , Ciclização , Dioxolanos/química , Lignanas/química , Estrutura Molecular , Naftalenos/química
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