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1.
J Org Chem ; 85(7): 4663-4671, 2020 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-32155066

RESUMO

A density functional theory (DFT) computational analysis, using the ωB97X-D functional, of a rapid amide cleavage in 2-carboxyphthalanilic acid (2CPA), where the amide group is flanked by two catalytic carboxyls, reveals key mechanistic information: (a) General base catalysis by a carboxylate coupled to general acid catalysis by a carboxyl is not operative. (b) Nucleophilic attack by a carboxylate on the amide carbonyl coupled to general acid catalysis at the amide oxygen can also be ruled out. (c) A mechanistic pathway that remains viable involves general acid proton delivery to the amide nitrogen by a carboxyl, while the other carboxylate engages in nucleophilic attack upon the amide carbonyl; a substantially unchanged amide carbonyl in the transition state; two concurrent bond-forming events; and a spatiotemporal-base rate acceleration. This mechanism is supported by molecular dynamic simulations which confirm a persistent key intramolecular hydrogen bonding. These theoretical conclusions, although not easily verified by experiment, are consistent with a bell-shaped pH/rate profile but are at odds with hydrolysis mechanisms in the classic literature.

2.
J Org Chem ; 84(15): 9684-9692, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31283216

RESUMO

The study of host-guest complexation between reactive 2-carboxyphthalanilic acid (CPA) and two cationic pillararenes has been carried out. Host-guest complexation with significant kinetic effects was observed only with the smaller cavity size pillararene (P5A). Kinetics in the pH range 1.50-6.40, ESI-MS, 1H NMR titration, and ROESY experiments were performed to characterize the complexes. High binding stoichiometry (H:G2) was observed for all CPA protonation states. The system is pH-dependent, and inversion of cooperativity (negative to positive) occurs by increasing the dianionic CPA2- concentration (allosteric behavior). Toward physiological pH, association constant K1:1 does not change (104 M-1), and K1:2 increased from 102 to 104 M-1, as well as the inhibitory effect increased up to 222-fold. NMR results elucidated the structure of the complex and allowed us to create a map of H-H interactions that describes well the diversity and number of interactions in the complex.

3.
An. acad. bras. ciênc ; 89(3): 1907-1915, July-Sept. 2017. tab
Artigo em Inglês | LILACS | ID: biblio-886748

RESUMO

ABSTRACT Many essential oils (EOs) of different plant species possess interesting antimicrobial effects on buccal bacteria and antioxidant properties. Eugenia klotzschiana Berg (pêra-do-cerrado, in Portuguese) is a species of Myrtaceae with restricted distribution in the Cerrado. The essential oils were extracted through the hydrodistillation technique using a modified Clevenger apparatus (2 hours) and chemically characterized by GC-MS. The major compounds were α-copaene (10.6 %) found in oil from leaves in natura, β-bisabolene (17.4 %) in the essential oil from dry leaves and α-(E)-bergamotene (29.9 %) in oil from flowers. The antioxidant activity of essential oils showed similarities in both methods under analysis (DPPH and ABTS˙+) and the results suggested moderate to high antioxidant activity. The antibacterial activity was evaluated by determining minimum inhibitory concentrations (MICs), using the microdilution method. MIC values below 400 µg/mL were obtained against Streptococcus salivarius (200 µg/mL), S. mutans (50 µg/mL), S. mitis (200 µg/mL) and Prevotella nigrescens (50 µg/mL). This is the first report of the chemical composition and antibacterial and antioxidant activities of the essential oils of E. klotzschiana. These results suggest that E. klotzschiana, a Brazilian plant, provide initial evidence of a new and alternative source of substances with medicinal interest.


Assuntos
Streptococcus/efeitos dos fármacos , Prevotella/efeitos dos fármacos , Folhas de Planta/química , Flores/química , Eugenia/química , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Testes de Sensibilidade Microbiana , Cromatografia Gasosa-Espectrometria de Massas , Antibacterianos/isolamento & purificação , Antioxidantes/isolamento & purificação
4.
An Acad Bras Cienc ; 89(3): 1907-1915, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28767890

RESUMO

Many essential oils (EOs) of different plant species possess interesting antimicrobial effects on buccal bacteria and antioxidant properties. Eugenia klotzschiana Berg (pêra-do-cerrado, in Portuguese) is a species of Myrtaceae with restricted distribution in the Cerrado. The essential oils were extracted through the hydrodistillation technique using a modified Clevenger apparatus (2 hours) and chemically characterized by GC-MS. The major compounds were α-copaene (10.6 %) found in oil from leaves in natura, ß-bisabolene (17.4 %) in the essential oil from dry leaves and α-(E)-bergamotene (29.9 %) in oil from flowers. The antioxidant activity of essential oils showed similarities in both methods under analysis (DPPH and ABTS˙+) and the results suggested moderate to high antioxidant activity. The antibacterial activity was evaluated by determining minimum inhibitory concentrations (MICs), using the microdilution method. MIC values below 400 µg/mL were obtained against Streptococcus salivarius (200 µg/mL), S. mutans (50 µg/mL), S. mitis (200 µg/mL) and Prevotella nigrescens (50 µg/mL). This is the first report of the chemical composition and antibacterial and antioxidant activities of the essential oils of E. klotzschiana. These results suggest that E. klotzschiana, a Brazilian plant, provide initial evidence of a new and alternative source of substances with medicinal interest.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Eugenia/química , Flores/química , Folhas de Planta/química , Prevotella/efeitos dos fármacos , Streptococcus/efeitos dos fármacos , Antibacterianos/isolamento & purificação , Antioxidantes/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Testes de Sensibilidade Microbiana
5.
BMC Cell Biol ; 9: 68, 2008 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-19087356

RESUMO

BACKGROUND: As an obligatory intracellular parasite, Trypanosoma cruzi, the etiological agent of Chagas' disease, must invade and multiply within mammalian cells. Cytokeratin 18 (CK18) is among the host molecules that have been suggested as a mediator of important events during T. cruzi-host cell interaction. Based on that possibility, we addressed whether RNA interference (RNAi)-mediated down regulation of the CK18 gene could interfere with the parasite life cycle in vitro. HeLa cells transiently transfected with CK18-RNAi had negligible levels of CK18 transcripts, and significantly reduced levels of CK18 protein expression as determined by immunoblotting or immunofluorescence. RESULTS: CK18 negative or positive HeLa cells were invaded equally as well by trypomastigotes of different T. cruzi strains. Also, in CK18 negative or positive cells, parasites recruited host cells lysosomes and escaped from the parasitophorous vacuole equally as well. After that, the growth of amastigotes of the Y or CL-Brener strains, was drastically arrested in CK18 RNAi-treated cells. After 48 hours, the number of amastigotes was several times lower in CK18 RNAi-treated cells when compared to control cells. Simultaneous staining of parasites and CK18 showed that in HeLa cells infected with the Y strain both co-localize. Although the amastigote surface protein-2 contains the domain VTVXNVFLYNR previously described to bind to CK18, in several attempts, we failed to detect binding of a recombinant protein to CK-18. CONCLUSION: The study demonstrates that silencing CK18 by transient RNAi, inhibits intracellular multiplication of the Y and CL strain of T. cruzi in HeLa cells, but not trypanosome binding and invasion.


Assuntos
Doença de Chagas/metabolismo , Doença de Chagas/parasitologia , Interações Hospedeiro-Patógeno/genética , Queratina-18/genética , Interferência de RNA , Trypanosoma cruzi/patogenicidade , Animais , Adesão Celular/genética , Doença de Chagas/genética , Replicação do DNA/genética , DNA de Protozoário/genética , Regulação para Baixo , Células HeLa , Humanos , Queratina-18/metabolismo , Lisossomos/genética , Fagocitose/genética , RNA Interferente Pequeno/genética , Especificidade da Espécie , Transfecção , Trypanosoma cruzi/fisiologia , Virulência/genética
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