A AÇÃO DOS METAIS PESADOS PROVENIENTES DE REJEITOS DE MINERAÇÃO SOBRE A SAÚDE E O MEIO AMBIENTE

O presente artigo traz uma revisão da literatura abordando os principais impactos do despejo irregular dos rejeitos provenientes da extração mineral, principalmente, em relação aos três metais pesados: Mercúrio, Arsênio e Cádmio. A atividade de mineração possui um grande papel no contexto nacional, com elevada importância para o crescimento do país, desde que seja sempre realizada de modo sustentável, garantindo e preservando o bem-estar da sociedade como um todo. O despejo irregular desses rejeitos pode levar a sérios danos à saúde, ao ambiente e a economia, trazendo agravos principalmente à população residente próximo a zonas contaminadas. Para tanto, torna-se fundamental um planejamento adequado para o descarte desses rejeitos, a fim de prevenir e diminuir os impactos ambientais causados

Computational Studies of Benzoxazinone Derivatives as Antiviral Agents against Herpes Virus Type 1 Protease

Herpes simplex virus infections have been described in the medical literature for centuries, yet the the drugs available nowadays for therapy are largely ineffective and low oral bioavailability plays an important role on the inefficacy of the treatments. Additionally, the details of the inhibition of Herpes Virus type 1 are still not fully understood. Studies have shown that several viruses encode one or more proteases required for the production new infectious virions. This study presents an analysis of the interactions between HSV-1 protease and benzoxazinone derivatives through a combination of structure-activity relationships, comparative modeling and molecular docking studies. The structure activity relationship results showed an important contribution of hydrophobic and polarizable groups and limitations for bulky groups in specific positions. Two Herpes Virus type 1 protease models were constructed and compared to achieve the best model which was obtained by MODELLER. Molecular docking results pointed to an important interaction between the most potent benzoxazinone derivative and Ser129, consistent with previous mechanistic data. Moreover, we also observed hydrophobic interactions that may play an important role in the stabilization of inhibitors in the active site. Finally, we performed druglikeness and drugscore studies of the most potent derivatives and the drugs currently used against Herpes virus

Synthesis, Cytotoxicity and Mechanistic Evaluation of 4-Oxoquinoline-3-carboxamide Derivatives: Finding New Potential Anticancer Drugs

Made available in DSpace on 2015-05-04T16:34:31Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) floriano_silvajretal_IOC_2014.pdf: 1412917 bytes, checksum: efe4a373bbf1ee3722bc9e0e8338d523 (MD5) Previous issue date: 2014Universidade Federal Fluminense. Outeiro de São João Batista. Niterói, Brasil.Universidade Federal Fluminense. Outeiro de São João Batista. Niterói, Brasil.Universidade Federal do Rio de Janeiro. Laboratório de Modelagem Molecular e 3D QSAR (ModMolQSAR). Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. LABIEMol. Outeiro de São João Batista. Niterói, RJ, Brasil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Belém, PA, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Proteinas e Peptídeos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Proteinas e Peptídeos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Proteinas e Peptídeos. Rio de Janeiro, RJ, Brasil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Belém, PA, Brasil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Belém, PA, Brasil.Universidade Federal do Rio de Janeiro. Laboratório de Modelagem Molecular e 3D QSAR (ModMolQSAR). Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Laboratório de Modelagem Molecular e 3D QSAR (ModMolQSAR). Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Outeiro de São João Batista. Niterói, Brasil.Universidade Federal Fluminense. Outeiro de São João Batista. Niterói, Brasil.Universidade Federal Fluminense. Outeiro de São João Batista. Niterói, Brasil.Universidade Federal Fluminense. Outeiro de São João Batista. Niterói, Brasil.As part of a continuing search for new potential anticancer candidates, we describe the synthesis, cytotoxicity and mechanistic evaluation of a series of 4-oxoquinoline-3-carboxamide derivatives as novel anticancer agents. The inhibitory activity of compounds 10–18 was determined against three cancer cell lines using the MTT colorimetric assay. The screening revealed that derivatives 16b and 17b exhibited significant cytotoxic activity against the gastric cancer cell line but was not active against a normal cell line, in contrast to doxorubicin, a standard chemotherapeutic drug in clinical use. Interestingly, no hemolytical activity was observed when the toxicity of 16b and 17b was tested against blood cells. The in silico and in vitro mechanistic evaluation indicated the potential of 16b as a lead for the development of novel anticancer agents against gastric cancer cells