Synthesis and evaluation of 2-phenylamino-1,4-naphthoquinones derivatives as potential hypoglycaemic agents

Abstract Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of chloro group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.

Resumo Em razão dos graves efeitos colaterais causados pela maioria dos medicamentos antidiabéticos atualmente utilizados, continua a busca por novos medicamentos seguros para o controle do diabetes. As naftoquinonas, que possuem fortes propriedades antioxidantes, têm sido empregadas como candidatas à terapia do diabetes. O presente estudo visa encontrar o potencial antioxidante e hipoglicemiante de alguns novos derivados de 2-fenilamino-1,4-naftoquinonas (PAN), incluindo derivados de cloro, nitro, metil e bromo (5a-d) sintetizados por experimento em pote único. Os cristais do produto foram purificados por TLC e caracterizados por FT-IR. O potencial antioxidante dos compostos foi testado por meio de atividades de sequestro de radicais DPPH e redução de energia observada como absorção no UV-vis. O ensaio DPPH mostrou a poderosa atividade antioxidante dos derivados nitro e bromo, enquanto o derivado nitro mostrou o potencial de redução significativo para o ensaio FRAP. O potencial hipoglicêmico dos compostos foi estudado em modelo animal de rato. Todos os compostos sintetizados revelaram melhor atividade hipoglicemiante; no entanto, o derivado cloro apresentou atividade hipoglicêmica mais potente, com redução de 43% nos níveis médios de glicose no sangue dos animais tratados. Como a biorredução de naftoquinonas pode ser influenciada pela alteração de suas propriedades redox, notou-se que o efeito da doação eletrônica por ressonância (+R) do grupo cloro tem sido significativo na atividade biológica por meio da estabilização de sua forma imina, que limita o potencial de geração de radicais livres durante a biorredução de quinonas, e, portanto, tem sido proposto como a razão de sua atividade hipoglicemiante. Estudos futuros empregando as propriedades de grupos de doação eletrônica de PAN podem otimizar a interação droga-receptor para melhor planejamento de medicamentos e estratégias de desenvolvimento de medicamentos contra o diabetes e também para os ensaios clínicos.

Synthesis and evaluation of 2-phenylamino-1, 4-naphthoquinones derivatives as potential hypoglycaemic agents / Síntese e avaliação de derivados de 2-fenilamino-1, 4-naftoquinonas como potenciais agentes hipoglicemiantes

Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of 'chloro' group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.

Em razão dos graves efeitos colaterais causados pela maioria dos medicamentos antidiabéticos atualmente utilizados, continua a busca por novos medicamentos seguros para o controle do diabetes. As naftoquinonas, que possuem fortes propriedades antioxidantes, têm sido empregadas como candidatas à terapia do diabetes. O presente estudo visa encontrar o potencial antioxidante e hipoglicemiante de alguns novos derivados de 2-fenilamino-1,4-naftoquinonas (PAN), incluindo derivados de cloro, nitro, metil e bromo (5a-d) sintetizados por experimento em pote único. Os cristais do produto foram purificados por TLC e caracterizados por FT-IR. O potencial antioxidante dos compostos foi testado por meio de atividades de sequestro de radicais DPPH e redução de energia observada como absorção no UV-vis. O ensaio DPPH mostrou a poderosa atividade antioxidante dos derivados nitro e bromo, enquanto o derivado nitro mostrou o potencial de redução significativo para o ensaio FRAP. O potencial hipoglicêmico dos compostos foi estudado em modelo animal de rato. Todos os compostos sintetizados revelaram melhor atividade hipoglicemiante; no entanto, o derivado cloro apresentou atividade hipoglicêmica mais potente, com redução de 43% nos níveis médios de glicose no sangue dos animais tratados. Como a biorredução de naftoquinonas pode ser influenciada pela alteração de suas propriedades redox, notou-se que o efeito da doação eletrônica por ressonância (+R) do grupo "cloro" tem sido significativo na atividade biológica por meio da estabilização de sua forma imina, que limita o potencial de geração de radicais livres durante a biorredução de quinonas, e, portanto, tem sido proposto como a razão de sua atividade hipoglicemiante. Estudos futuros empregando as propriedades de grupos de doação eletrônica de PAN podem otimizar a interação droga-receptor para melhor planejamento de medicamentos e estratégias de desenvolvimento de medicamentos contra o diabetes e também para os ensaios clínicos.

Synthesis and evaluation of 2-phenylamino-1,4-naphthoquinones derivatives as potential hypoglycaemic agents.

Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of 'chloro' group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.

Spatial and temporal variability of source contributions to ambient PM10 during winter in Augsburg, Germany using organic and inorganic tracers.

Daily PM10 samples were collected during a one-month sampling campaign from February 13 to March 12, 2008 at eight different sampling sites in Augsburg, Southern Germany. Source apportionment was performed to identify the main sources and related contributions by analysis of organic and inorganic tracers. Nine factors were separated comprising: solid fuel combustion, traffic-related emissions, secondary inorganics, and mixed sources. Spatiotemporal variation of the source contributions was evaluated using the Pearson correlation coefficient (r) and coefficient of divergence (COD). All factors (except hopanes and mixed sources) showed moderate to high (0.60.8) correlation coefficients between the eight sites and were distributed heterogeneously. Secondary sulfate and secondary nitrate factors were relatively more uniformly distributed (compared to other factors) with lower medians of COD value (0.47 and 0.56, respectively) and higher correlation values (r=0.97 and 0.85, respectively). The maximum daily average contribution for coal & wood combustion factor was observed at the LfU suburban site (4.0 µg m(-3)); wood combustion factor at the LSW residential site (5.1 µg m(-3)) ; diesel & fuel oil consumption factor at the Bifa suburban and BP urban sites (both 2.5 µg m(-3)); road dust & tram factor at the KP traffic site (16.2 µg m(-3)) and the BP urban site (6.6 µg m(-3)); hopanes factor at the BP urban and Bifa suburban sites (both 0.7 µg m(-3)); and de-icing NaCl factor at the KP traffic site (4.8 µg m(-3)). Secondary sulfate and secondary nitrate factors had approximately similar contributions (6.2 µg m(-3) and 4.3 µg m(-3), respectively) at all sites. Mixed sources factor had the highest daily average contribution to PM10 mass at the KP traffic site (7.0 µg m(-3)).

Concentrations and source contributions of particulate organic matter before and after implementation of a low emission zone in Munich, Germany.

Within the Munich low emission zone (LEZ), samples of PM(2.5) were collected before (2006/2007) and after (2009/2010) the implementation of the LEZ. The samples were analyzed for carbon fraction (EC/OC) and particulate organic compounds (POC). Significant lower concentrations were noticed for elemental carbon (EC) and some of the POC like vanillic acid, acetosyringone, syringylacetone and syringic acid after the implementation of the LEZ. Higher concentrations of levoglucosan, retene and O-PAH were detected in the second sampling period. Positive matrix factorization (PMF) was used to identify the main sources of POC. Emissions from traffic, solid fuels combustion, cooking and mixed source were separated. The contribution of traffic source factor was decreased about 60% after the implementation of the LEZ. Thus the average concentration of EC from traffic factor decreased from 1.1 to 0.5 µg/m(3) after the implementation of the LEZ.

Laser decompression of the facial nerve.

Laser decompression of the facial nerve is an experimental approach to evaluating the parameters for laser usage at a nerve-bone interface. This article summarizes the anatomic considerations and indications for facial nerve decompression, and the advantages and disadvantages of laser decompression of the facial nerve. Preliminary studies using the Vanderbilt free electron laser are described, and future directions for research are outlined.

Use of the holmium: yttrium aluminum garnet (Ho:YAG) laser for cranial nerve decompression: an in vivo study using the rabbit model.

A study was designed to evaluate the utility and safety of the holmium:yttrium aluminum garnet (Ho:YAG) laser for precise bony decompression of neural canals. In vivo rabbit studies were performed to measure temperature changes and nerve degeneration which occurred when the facial canal was decompressed with the laser as compared to the diamond burr. Marked temperature elevations were noted with the laser (n = 4), but not with the burr (n = 4). Seven of nine nerves decompressed with the laser revealed moderate to severe degeneration, whereas two control nerves decompressed with the drill demonstrated only minimal degeneration. It is concluded that this laser should not be used for nerve decompression unless better control of temperature elevation can be achieved.