RESUMO
A catalyst free ultrasound-assisted regio-/stereoselective modular approach was accomplished for the synthesis of highly constrained indenoquinoxaline engrafted spiro pyrrolidines from easily available substrates. This one-pot strategy utilizes 1,3-dipolar cycloaddition from a four component reaction of ninhydrin, 1,2-phenylenediamine, ß-nitrostyrene and benzylamine or amino acids under ultrasound irradiation. The transformation is mild and operationally simple, providing architecturally complex fused spiro polycyclic heterocycles. This synthesis was confined to follow the group-assistant-purification (GAP) chemistry process, which can avoid chromatographic purifications and use of catalysts and allows easy access to a novel class of spiro engrafted polyheterocyclic scaffolds, which may be beneficial in biomedical research/materials science in the near future. This opens an era for the formation of a single exo product, when compared with reported protocols, by merely switching over reaction conditions to US irradiation.
RESUMO
A series of new phenyl acetylene and isoxazole analogues of arjunolic acid were designed, synthesized and evaluated (3-8) for their tyrosinase and alpha glucosidase inhibitory potential. All the tested analogues exhibited stronger inhibitory activity than the standard drug or parent compound. Of these, compound (7) displayed the most potent tyrosinase inhibitory action with IC50 (14.3 ± 7.6) of about three folds more than the standard drug, kojic acid (41.5 ± 1.0). Further, compound (8) (14.5 ± 0.15) possessed the potent alpha glucosidase inhibitory action with IC50 value comparable to that of standard, acarbose (10.4 ± 0.06). Henceforth, compounds (7) and (8) are promising candidates for further studies.
Assuntos
Agaricales , Inibidores de Glicosídeo Hidrolases , Inibidores de Glicosídeo Hidrolases/farmacologia , Monofenol Mono-Oxigenase , Estrutura Molecular , Relação Estrutura-Atividade , alfa-Glucosidases/metabolismo , Simulação de Acoplamento Molecular , Agaricales/metabolismo , Alcinos , Desenho de FármacosRESUMO
Highly efficient methodology was developed for the construction of functionalized Kojic acid involving Click linker via 1,3-dipolar cycloaddition and their cytotoxicity against MCF-7, MIAPaCa-2 and DU145 mammalian cell lines were evaluated. Preliminary studies on structure-activity-relationship (SAR) revealed that substitution at C-2 of kojic acid as well as C-5 of 1,2,3-triazole motif played a major role in the activity profile. Kojic acid 1,2,3-triazole analogue 3 b containing an alkyl chain (n = 6) exhibited two fold potent activity than the parent compound, kojic acid against MCF-7 and MIA PaCa-2 cell lines. It induced apoptosis in these cell lines via ID1/PARP1 mediated pathway. The structures of the new analogues of kojic acid 1,2,3-triazole were confirmed by the detailed spectroscopic data analysis.
Assuntos
Antineoplásicos , Citotoxinas , Animais , Estrutura Molecular , Citotoxinas/farmacologia , Relação Estrutura-Atividade , Triazóis/química , Antineoplásicos/química , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , MamíferosRESUMO
A new steroidal ester bearing n-nonadecanoyl moiety (1) and a mixture of isomeric cerebrosides (2) along with two known compounds were isolated from the methanol extract of the stem-bark of Anacardium occidentale. The structure of the new steroidal ester was determined as 3-n-nonadecanoyl-ß-sitosterol on the basis of modern spectroscopic techniques (IR, ESI-MS, HR-ESIMS, 1D and 2D NMR) and chemical degradation studies. The structures of the known compounds were identified as gallic acid and tanacetene by comparison of the spectroscopic data with those of reported data. The mixture of cerebrosides was confirmed based on the analysis of 1D and 2D NMR. These compounds were evaluated for cytotoxicity against human cancer cell lines A549, SCOV3 and rat normal cell line NRK49f.
Assuntos
Anacardium/química , Casca de Planta/química , Caules de Planta/química , Sitosteroides/isolamento & purificação , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular Tumoral , Humanos , Concentração Inibidora 50 , Extratos Vegetais/química , Espectroscopia de Prótons por Ressonância Magnética , Ratos , Sitosteroides/farmacologiaRESUMO
Chemical manipulation studies were conducted on betulinic acid (1), twenty-one new rationally designed analogues of 1 with modifications at C-28 were synthesized for their evaluation of inhibitory effects on α-glucosidase and LPS-stimulated nitric oxide production in mouse macrophage RAW 264.7 cells. Compound 2 (IC50 = 5.4 µM) exhibited an almost 1.4-fold increase in α-glucosidase inhibitory activity on yeast α-glucosidase while analogues 5 (IC50 16.4 µM) and 11 (IC50 16.6 µM) exhibited a 2-fold enhanced inhibitory activity on NO-production than betulinic acid.
Assuntos
Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Óxido Nítrico/biossíntese , Triterpenos/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Inibidores de Glicosídeo Hidrolases/síntese química , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Triterpenos Pentacíclicos , Células RAW 264.7 , Relação Estrutura-Atividade , alfa-Glucosidases/metabolismo , Ácido BetulínicoRESUMO
The total syntheses of four polyketides, surinone B (1), alatanones A-B (2-3), and trineurone A (4) were accomplished through an efficient and unified strategy via one-pot C-acylation reaction coupling 1,3-cyclohexadiones with EDC-activated acids under mild conditions. Alatanone A (2) was found to be a potent anti-microbial agent against Gram-positive and Gram-negative bacteria with MIC 31.25 µg/ml while alatanone B (3) was found to be a potent anti-fungal agent against Cladosporium cladosporioides with MIC 62.5 µg/ml compared to cycloheximide MIC 125 µg/ml. Our methodology allows performing kilogram scale of these scarce polyketides for the development of new antimicrobials.
Assuntos
Policetídeos/síntese química , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Cladosporium/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Policetídeos/químicaRESUMO
The biotransformation of the front-line antimalarial drug, artemisinin (1) by the filamentous fungus Aspergillus flavus MTCC-9167 was investigated. Incubation of compound 1 with A. flavus afforded a new hydroxy derivative (2) along with three known metabolites (3-5). The new compound was characterized as 14-hydroxydeoxyartemisinin (2) by extensive spectroscopic data analysis (IR, 1H and 13C NMR, HSQC, HMBC, COSY, NOESY, and HR-ESIMS). The known metabolites were identified as deoxyartemisinin (3), artemisinin G (4), and 4α-hydroxydeoxyartemisinin (5). This is the first report of hydroxylation of a secondary methyl of artemisinin at C-14 by the fungus A. flavus, which is synthetically not accessible. In addition, these compounds were evaluated for their in vitro antiplasmodial activity. Artemisinin G (4) exhibited IC50 values in the submicromolar range, which was better than those of the nonperoxidic metabolites.
Assuntos
Artemisininas/química , Artemisininas/metabolismo , Aspergillus flavus/metabolismo , Antimaláricos/química , Antimaláricos/metabolismo , Biotransformação , Hidroxilação , Espectroscopia de Ressonância Magnética , Estrutura MolecularRESUMO
Phytochemical investigation into the CHCl3 extract of the fruits of Barringtonia racemosa resulted in the isolation of two new metabolites along with isoracemosol A and betulinic acid as known metabolites. The new compounds were characterised as phytosphingosine-type ceramide [(2S,3S,4R)-2-[(2R)-2-hydroxyhexadecanoyl amino]-hexacos-8(E)-ene-1,3,4-triol, 1] and racemosol E [21ß-acetoxy-22α-(2-methylbutyroxy)-olean-12-ene-3ß,16α,28-triol, 2] on the basis of extensive spectroscopic data analysis and chemical modifications. In addition, the self-gelating property of isoracemosol A (3) was investigated for the first time, which leads to the unexpected agglomerated porous-like morphology.
Assuntos
Barringtonia/química , Extratos Vegetais/química , Bibenzilas , Ceramidas/química , Frutas/química , Géis/química , Espectroscopia de Ressonância Magnética , Ácido Oleanólico/análogos & derivados , Porosidade , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Excolides A-B (1-4) represent the first examples of a new class of secolabdanoids with an unprecedented framework, which were isolated from the stems of Excoecaria agallocha. Their structures were determined by spectroscopic analysis, chemical modifications, CD, and single-crystal X-ray analysis (1 and 4) as excolide A (1), 11-epi-excolide A (2), 11,13-di-epi-excolide A (3), and excolide B (4). In addition, the structure of rhizophorin A (7), a novel bicyclic secolabdanoid, was revised as excolide A (1).