Convenient enzymatic resolution of (R,S)-2-methylbutyric acid catalyzed by immobilized lipases.

The application of several immobilized lipases has been explored in the enantioselective esterification of (R,S)-2-methylbutyric acid, an insect pheromone precursor. With the use of Candida antarctica B, using hexane as solvent, (R)-pentyl 2-methylbutyrate was prepared in 2 h with c 40%, eep 90%, and E = 35, while Thermomyces lanuginosus leads to c 18%, eep 91%, and E = 26. The (S)-enantiomer was obtained by the use of Candida rugosa or Rhizopus oryzae (2-h reaction, c 34% and 35%, eep 75 and 49%, and E = 10 and 4, respectively). Under optimal conditions, the effect of the solvent, the molar ratio, and the nucleophile were evaluated.

Enzymatic reactions involving the heteroatoms from organic substrates.

Several enzymatic reactions of heteroatom-containing compounds have been explored as unnatural substrates. Considerable advances related to the search for efficient enzymatic systems able to support a broader substrate scope with high catalytic performance are described in the literature. These reports include mainly native and mutated enzymes and whole cells biocatalysis. Herein, we describe the historical background along with the progress of biocatalyzed reactions involving the heteroatom(S, Se, B, P and Si) from hetero-organic substrates.

Finding the switch: turning a baeyer-villiger monooxygenase into a NADPH oxidase.

By a targeted enzyme engineering approach, we were able to create an efficient NADPH oxidase from a monooxygenase. Intriguingly, replacement of only one specific single amino acid was sufficient for such a monooxygenase-to-oxidase switch-a complete transition in enzyme activity. Pre-steady-state kinetic analysis and elucidation of the crystal structure of the C65D PAMO mutant revealed that the mutation introduces small changes near the flavin cofactor, resulting in a rapid decay of the peroxyflavin intermediate. The engineered biocatalyst was shown to be a thermostable, solvent tolerant, and effective cofactor-regenerating biocatalyst. Therefore, it represents a valuable new biocatalytic tool.

Antitumoral activity of a trichloromethyl pyrimidine analogue: molecular cross-talk between intrinsic and extrinsic apoptosis.

Acute lymphoblastic leukemia (ALL) is a malignant disorder caused by the proliferation of lymphoid progenitor cells and is the most common cancer in children. Cytotoxic nucleoside analogues are important chemotherapeutic agents, which are used in many cancers, including leukemias. In this study, we investigated the effects of the synthetic nucleoside analogue 1-(5,5,5-trichloro-2-methoxy-4-oxopenten-2-yl)-4-trichloromethyl-pyrimidin-2(1H)-one, named compound 3 or C3, on leukemia cell lines. The compound stimulated cell death by apoptosis, evidenced by DNA fragmentation, phosphatidylserine externalization, and caspase-3 activation. Compound 3 seemed to trigger several cell death pathways. The mitochondrial pathway was evidenced through a disturbance of mitochondrial membrane potential, strong cytochrome c liberation, decrease of antiapoptotic Bcl-2 protein expression, and caspase-9 activation. The C3 also induced caspase-8 and -12 activation, an increase in the intracellular calcium level, and an overproduction of reactive oxygen species. Increased caspase 8 activity suggests that the extrinsic pathway was activated and that the ROS production and enzyme activity alteration (glutathione S-transferase, glutathione peroxidase, catalase, and glutathione reductase) might be related to oxidative stress. Finally, the increase in calcium release, CHOP expression, and caspase-12 activity might characterize endoplasmic reticulum stress. Compound 3 was likewise cytotoxic to leukemic and melanoma human cell lines. Taken together, the results contribute to further understanding the new pyrimidine analogue as a potential chemotherapeutic drug or lead molecule.

Molecular Docking and Quantum Studies of Lawsone Dimers Derivatives: New Investigation of Antioxidant Behavior and Antifungal Activity.

BACKGROUND: In general, fungal species are characterized by their opportunistic character and can trigger various infections in immunocompromised hosts. The emergence of infections associated with high mortality rates is due to the resistance mechanisms that these species develop. METHODS: This phenomenon of resistance denotes the need for the development of new and effective therapeutic approaches. In this paper, we report the investigation of the antioxidant and antifungal behavior of dimeric naphthoquinones derived from lawsone whose antimicrobial and antioxidant potential has been reported in the literature. RESULTS: Seven fungal strains were tested, and the antioxidant potential was tested using the combination of the methodologies: reducing power, total antioxidant capacity and cyclic voltammetry. Molecular docking studies (PDB ID 5V5Z and 1EA1) were conducted which allowed the derivation of structureactivity relationships (SAR). Compound 1-i, derived from 3-methylfuran-2-carbaldehyde showed the highest antifungal potential with an emphasis on the inhibition of Candida albicans species (MIC = 0.5 µg/mL) and the highest antioxidant potential. CONCLUSION: A combination of molecular modeling data and in vitro assays can help to find new solutions to this major public health problem.

Um programa de mentoria para estudantes de Medicina de uma universidade do Centro-Oeste brasileiro / A mentoring program for medicine students at a University inthe Midwest of Brazil

Resumo: Introdução: Neste artigo, fazemos um relato de experiência da implantação e do funcionamento de um programa de mentoria aplicado a estudantes de graduação do curso de Medicina de uma universidade do Centro-Oeste brasileiro. É consenso que a pressão dos cursos de Medicina provoca sobrecarga emocional e afeta negativamente os estudantes, e é preciso que medidas de apoio sejam implementadas. Relato de experiência: O programa de mentoria da Faculdade de Medicina da Universidade Federal de Goiás teve um processo de construção lógico. Foi criado no início de 2015, pelo reconhecimento da necessidade da instituição em apoiar os acadêmicos durante sua graduação, fato evidenciado a partir do atendimento psicológico ao aluno e de uma pesquisa in loco. Os seguintes aspectos-chave caracterizam o programa: é oferecido como uma disciplina eletiva, pode ser feito até cinco vezes e,além de um encontro mensal com o mentor, o estudante escolhe as oficinas de que deseja participar, diversificando assim sua formação. Após 12 semestres de funcionamento, sintetizamos neste artigo uma parte de nossos resultados e algumas reflexões sobre o que queremos para o futuro do programa. Discussão: A implementação da mentoria e suas adequações foram resultados de pesquisa, capacitação, discussões dos docentes e avaliação periódica pelos mentorados. As mudanças procuraram atender às expectativas e sugestões dos estudantes, objetivando atrair a atenção e satisfazer aos anseios dos discentes. Ao longo dos 12 semestres de funcionamento do programa, o interesse dos alunos pela matrícula na disciplina cresceu, com forte avaliação positiva, especialmente pela livre escolha e diversidade de oficinas, e pelo envolvimento do tutor. Conclusão: As instituições de ensino devem estimular a criação de programas de mentoria. O programa relatado neste artigo tem tido boa aceitação por parte dos alunos e nos aponta bons resultados.

Abstract: Introduction: This article reports on the experience of implementing and running a mentoring program for medical school students at a Brazilian university in the Midwest region. It is widely accepted that the pressure at medical school is detrimental to the students and often leads to emotional overload. Therefore, supporting mechanisms must be implemented. Experience report: The mentoring program at the Federal University of Goiás had a logical beginning. It was created in early 2015, after psychotherapy services offered to the students led to an in loco research study, which in turn pointed out the need to provide support to students throughout their undergraduate studies. There are some key characteristic aspects of the program: it's an elective course, which can be taken up to 5 times, and the students can choose the workshops they want to attend in addition to the monthly meeting with the mentor, which allows for diverse paths to be followed. After twelve semesters in existence, this article presents a summary of some of the results obtained and reflections on the future of this program. Discussion: The implementation of the program and its adaptations resulted from research, professional development, discussions among professors and regular assessments by the mentees. Changes were made according to the expectations and suggestions of participating students, aiming to effectively meet their needs and represent a desirable course. Since its inception, the program has attracted increasingly more students, and enjoyed a strong positive evaluation, mainly due to the various workshops to choose from and engagement with the mentor. Conclusion: Universities should support the creation of such mentoring programs. The program discussed in this article has been well received and points towards positive outcomes.

Enzymatic reactions involving the heteroatoms from organic substrates

ABSTRACT Several enzymatic reactions of heteroatom-containing compounds have been explored as unnatural substrates. Considerable advances related to the search for efficient enzymatic systems able to support a broader substrate scope with high catalytic performance are described in the literature. These reports include mainly native and mutated enzymes and whole cells biocatalysis. Herein, we describe the historical background along with the progress of biocatalyzed reactions involving the heteroatom(S, Se, B, P and Si) from hetero-organic substrates.