RESUMO

Dapsone (DDS) is an antibacterial drug with well-known antioxidant properties. However, the antioxidant behavior of its derivatives has not been well explored. In the present work, the antioxidant activity of 10 dapsone derivatives 4-substituted was determined by an evaluation in two in vitro models (DPPH radical scavenging assay and ferric reducing antioxidant power). These imine derivatives 1-10 were obtained through condensation between DDS and the corresponding aromatic aldehydes 4-substuited. Three derivatives presented better results than DDS in the determination of DPPH (2, 9, and 10). Likewise, we have three compounds with better reducing activity than dapsone (4, 9, and 10). In order to be more insight, the redox process, a conceptual DFT analysis was carried out. Molecular descriptors such as electronic distribution, the total charge accepting/donating capacity (I/A), and the partial charge accepting/donating capacity (ω+/ω-) were calculated to analyze the relative donor-acceptor capacity through employing a donor acceptor map (DAM). The DFT calculation allowed us to establish a relationship between GAPHOMO-LUMO and DAM with the observed antioxidant effects. According to the results, we concluded that compounds 2 and 3 have the lowest Ra values, representing a good antioxidant behavior observed experimentally in DPPH radical capturing. On the other hand, derivatives 4, 9, and 10 display the best reducing capacity activity with the highest ω- and Rd values. Consequently, we propose these compounds as the best antireductants in our DDS imine derivative series.

Assuntos

Antioxidantes/síntese química , Dapsona/química , Iminas/síntese química , Antioxidantes/química , Antioxidantes/farmacologia , Simulação por Computador , Teoria da Densidade Funcional , Iminas/química , Iminas/farmacologia , Estrutura Molecular , Relação Estrutura-Atividade

RESUMO

Imine functionality is found in many compounds with important biological activity. Thus, the development of novel synthetic approaches for imines is important. In this work, it is propose an easy, eco-friendly and straightforward synthesis pathway of aryl imines under microwave irradiation catalyzed by Alumina-sulfuric acid. In addition, the in vitro enzymatic inhibition, antioxidant activity and molecular docking studies were performed. The aryl imines were isolated with yields in the range of 37-94%. All aryl imines synthesized were evaluated for in vitro inhibitory potential against α-glucosidase and α-amylase enzymes and the results exhibited that the most of the compounds displayed inhibitory activity against both enzymes. The (E)-1-(4-nitrophenyl)-N-(pyridin-2-yl)methanimine (3d) was 1.15-fold more active than acarbose against α-amylase whilst the (E)-1-phenyl-N-(pyridin-2-yl)methanimine (3c) displayed similar activity that acarbose against α-glucosidase. The molecular docking studies in α-glucosidase and α-amylase reveal that aryl imines mainly establish an H-bond with the R2-subtituent and hydrophobic interactions with the R1-subtituent. The docking analysis reveals these synthetic aryl imines 3d-i interact in same active site than acarbose drug in both enzymes.

Assuntos

Inibidores de Glicosídeo Hidrolases/farmacologia , Iminas/farmacologia , Simulação de Acoplamento Molecular , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo , Animais , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Iminas/síntese química , Iminas/química , Estrutura Molecular , Relação Estrutura-Atividade , Suínos , alfa-Amilases/metabolismo

RESUMO

Friedelan-3-one (1) and friedelane-3,16-dione (2) isolated from leaves and branches of Maytenus robusta Reissek were subjected to structural modifications via nucleophilic addition to the carbonyl group and Baeyer-Villiger oxidation in order to synthesize potential cytotoxic compounds. The oximes friedelane-3-hydroxyimino (3) and 3-hydroxyiminofriedelan-16-one (4) together with the lactones friedelane-3,4-lactone (5) and 3,4-lactonefriedelan-16-one (6) were characterized by IR and NMR spectroscopic analyses. Compounds 4 and 6 are reported for the first time. Cytotoxic screening via MTT assay in human leukemia cell lines (THP-1 and K562) demonstrated no significant improvement of compounds 3-6 when compared to the starting materials. Only compounds 3 and 5 demonstrated an improvement against K562 cells. However, the same assay on ovarian and breast cancer cell lines (TOV-21G and MDA-MB-231) showed a reduction in the IC50 for compounds 4-6, indicating that ring A modifications may enhance the biological potential.

Assuntos

Antineoplásicos/farmacologia , Celastraceae/química , Citotoxinas/isolamento & purificação , Iminas/química , Lactonas/química , Triterpenos/química , Antineoplásicos/síntese química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Citotoxinas/síntese química , Citotoxinas/farmacologia , Humanos , Iminas/síntese química , Lactonas/síntese química , Folhas de Planta/química , Relação Estrutura-Atividade , Triterpenos/isolamento & purificação

RESUMO

Phenylpyrazole insecticides are successful for crop protection and public hygiene by blocking gamma-aminobutyric acid (GABA)-gated chloride channels and glutamate-gated chloride (GluCl) channels. A series of novel phenylpyrazoles containing arylimine or 1-methoxyaryl groups were designed and synthesized. The addition reaction of methanol to the imines 1-11 was investigated and the cayno addition products 13-15 were obtained. The compounds 1-15 were confirmed by 1H NMR and elemental analysis. The results of bioassay indicated that some compounds exhibited comparable bioactivity to fipronil against a broad spectrum of insects such as bean aphid (Aphis craccivora), mosquito (Culex pipiens pallens), diamondback moth (Plutella xylostella) and Oriental armyworm (Mythimna separata). Especially, the foliar contact activity against bean aphid of compound 7 at 10 µg mL-1 was 68%, the larvacidal activity against mosquito of compounds 5, 13 and 15 at 0.0025 µg mL-1 was 100%, the larvacidal activity against diamondback moth of compounds 9 and 11 at 0.05 µg mL-1 was 100%, the larvacidal activity against Oriental armyworm of compound 9 at 1 µg mL-1 was 100%. The 3-cayno moiety on pyrazole ring was essential for the high insecticidal activities against bean aphid, diamondback moth and Oriental armyworm, while the 3-carbimidate moiety on pyrazole ring was crucial to the excellent high insecticidal activities against mosquito.

Assuntos

Iminas/toxicidade , Inseticidas/toxicidade , Pirazóis/toxicidade , Animais , Desenho de Fármacos , Iminas/síntese química , Insetos/efeitos dos fármacos , Inseticidas/síntese química , Larva/efeitos dos fármacos , Estrutura Molecular , Pirazóis/síntese química , Relação Estrutura-Atividade

RESUMO

An efficient one-step method to access 4(3H)quinazolinimines by reaction of phenylchloroimines with 2-aminobenzonitrile is described. The reaction of (E)-N-(2-cyanophenyl)benzimidoyl chloride with substituted anilines that yields a number of their corresponding C2, N3-substituted quinazoliniminium chlorides or neutral products is also reported. These methods provide direct and flexible access to diverse substituted iminoquinazolines substituted at the C2, N3-positions. All the new compounds were fully characterized and six examples are given with their single-crystal X-ray structure.

Assuntos

Aminas/química , Benzimidazóis/química , Iminas/síntese química , Nitrilas/química , Quinazolinas/síntese química , Iminas/química , Estrutura Molecular , Quinazolinas/química

RESUMO

Rifampicin, discovered more than 50 years ago, represents the last novel class of antibiotics introduced for the first-line treatment of tuberculosis. Drugs in this class form part of a 6-month regimen that is ineffective against MDR and XDR TB, and incompatible with many antiretroviral drugs. Investments in R&D strategies have increased substantially in the last decades. However, the number of new drugs approved by drug regulatory agencies worldwide does not increase correspondingly. Ruthenium complexes (SCAR) have been tested in our laboratory and showed promising activity against Mycobacterium tuberculosis. These complexes showed up to 150 times higher activity against MTB than its organic molecule without the metal (free ligand), with low cytotoxicity and high selectivity. In this study, promising results inspired us to seek a better understanding of the biological activity of these complexes. The in vitro biological results obtained with the SCAR compounds were extremely promising, comparable to or better than those for first-line drugs and drugs in development. Moreover, SCAR 1 and 4, which presented low acute toxicity, were assessed by Ames test, and results demonstrated absence of mutagenicity.

Assuntos

Antituberculosos/farmacologia , Complexos de Coordenação/farmacologia , Iminas/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Fosfinas/farmacologia , Ácidos Picolínicos/farmacologia , Rutênio/farmacologia , Animais , Antituberculosos/efeitos adversos , Antituberculosos/síntese química , Antituberculosos/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Humanos , Iminas/síntese química , Iminas/química , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Mutagênese/efeitos dos fármacos , Testes de Mutagenicidade , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/isolamento & purificação , Fosfinas/síntese química , Fosfinas/química , Ácidos Picolínicos/síntese química , Ácidos Picolínicos/química , Rutênio/química , Testes de Toxicidade Aguda

RESUMO

UNLABELLED: Cryptococcosis, a fungal infection that affects both immunocompromised and immunocompetent individuals, contributes to increasing indices of mortality and morbidity. The development of resistance by Cryptococcus spp., the limited number of commercial antifungal drugs and the various side effects of these drugs cause the treatment of cryptococcosis to be a challenge. The in vitro anticryptococcal activity of nine hydroxyaldimines was evaluated against 24 strains of Cryptococcus spp. Antifungal susceptibility was evaluated using a broth microdilution assay following the Clinical and Laboratory Standards Institute guidelines, using fluconazole as a positive control. Parameters such as the minimum inhibitory concentration and the minimum fungicidal concentration (MIC and MFC, respectively) were also determined. Antiproliferative activity on the normal cell line VERO was assessed 48 h post-compound exposure to determine the selectivity index (SI) of the hydroxyaldimines and fluconazole. All hydroxyaldimines were active against Cryptococcus spp. strains. Compounds 3A9 and 3B7 were the most potent against the Cryptococcus gattii and Cryptococcus neoformans strains. Selectivity indices also revealed that 3B10, 3C3, 3D3 and 3D9 are good candidates for in vivo studies. The in vitro anticryptococcal activity of hydroxyaldimines against various strains of C. gattii and C. neoformans indicates the potential of this class of molecules as lead compound for the development of selective and efficient anticryptococcal agents. SIGNIFICANCE AND IMPACT OF THE STUDY: The effectiveness of hydroxyaldimines for inhibition of Cryptococcus spp. growth and their low toxicity against healthy monkey kidney epithelial cells makes them promising lead compounds for the design of new anticryptococcal agents.

Assuntos

Antifúngicos/farmacologia , Cryptococcus gattii/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Iminas/farmacologia , Animais , Chlorocebus aethiops , Fluconazol/farmacologia , Iminas/síntese química , Iminas/química , Testes de Sensibilidade Microbiana , Células Vero

RESUMO

We modified the thiazolidinic ring at positions N3, C4, and C5, yielding compounds 6-24. Compounds with a phenyl at position N3, 15-19, 22-24, exhibited better inhibitory properties for cruzain and against the parasite than 2-iminothiazolidin-4-one 5. We were able to identify one high-efficacy trypanocidal compound, 2-minothiazolidin-4-one 18, which inhibited the activity of cruzain and the proliferation of epimastigotes and was cidal for trypomastigotes but was not toxic for splenocytes. Having located some of the structural determinants of the trypanocidal properties, we subsequently wished to determine if the exchange of the thiazolidine for a thiazole ring leaves the functional properties unaffected. We therefore tested thiazoles 26-45 and observed that they did not inhibit cruzain, but they exhibited trypanocidal effects. Parasite development was severely impaired when treated with 18, thus reinforcing the notion that this class of heterocycles can lead to useful cidal agents for Chagas disease.

Assuntos

Doença de Chagas/tratamento farmacológico , Iminas/síntese química , Tiazolidinas/síntese química , Tripanossomicidas/síntese química , Trypanosoma cruzi/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Simulação por Computador , Cisteína Endopeptidases/metabolismo , Feminino , Iminas/química , Iminas/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Ligação Proteica , Proteínas de Protozoários/antagonistas & inibidores , Proteínas de Protozoários/metabolismo , Baço/citologia , Estereoisomerismo , Relação Estrutura-Atividade , Tiazolidinas/química , Tiazolidinas/farmacologia , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/metabolismo

RESUMO

[reaction: see text] (-)-(5S)-2-Imino-1-methylpyrrolidine-5-carboxylic acid (1), previously reported as the N-acetyl-beta-d-glucosaminidase inhibitor pyrostatin B, has been isolated from the organic extracts of the burrowing sponge Cliona tenuis. The structure of 1, including its absolute stereochemistry, was characterized from its spectral data and chemical transformations and confirmed by total synthesis. The synthesis of 1 reveals that the structure of pyrostatin B has been incorrectly assigned. Comparison of NMR spectral data strongly suggests that pyrostatins A and B are identical to 5-hydroxyectoine and ectoine, respectively.

Assuntos

Diamino Aminoácidos/química , Iminas/química , Iminas/síntese química , Poríferos/química , Pirrolidinas/química , Pirrolidinas/síntese química , Animais , Iminas/isolamento & purificação , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Pirrolidinas/isolamento & purificação , Estereoisomerismo

RESUMO

Herein we describe the synthesis and spectroscopic (infrared and UV-vis) analysis of [Cu(II)(dohpn)(L)](n+) (dohpn=imineoximic tetraazamacrocyclic ligand 2,3,9,10-tetramethyl-1,4,8,11-tetraazaundecane-1,3,8,10-tetraen-11-ol-1-olate) and L=SCN(-), I(-), Cl(-) (n=0) and 4-aminopyridine (ampy), 4,4'-bipyridine (bipy), imidazole (im), 2-aminopyrazine (ampz) and water (n=1+). The following order of the Jahn-Teller stabilization energy (cm(-1)) was observed: I(-)(6452)

Assuntos

Cobre/química , Iminas/química , Compostos Organometálicos/química , Oximas/química , Iminas/síntese química , Compostos Organometálicos/síntese química , Oximas/síntese química , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta