In silico ADMET prediction, evaluation of cytotoxicity in mouse splenocytes and preliminary evaluation of in vitro antimalarial activity of 4-(4-chlorophenyl)thiazole compounds.

In this work, an in silico study and evaluation of the cytotoxicity of 4-(4-chlorophenyl)thiazole compounds against mouse splenocytes and the chloroquine-sensitive Plasmodium falciparum 3D7 strain are reported. The in silico results showed that the compounds have important pharmacokinetic properties for compounds with potential drug candidates. Regarding cytotoxicity assays against splenocytes, the compounds have low cytotoxicity. In addition, they were able to promote activation of these cells by increasing nitric oxide production without promoting cell death. Finally, they were able to promote cell proliferation. Regarding the in vitro anti-P. falciparum activity assays, it was observed that the compounds were able to inhibit the parasite's growth, presenting IC50 values ​​ranging from 0.79 to greater than 10 µM. These results are promising when compared to chloroquine. Therefore, this study showed that 4-(4-chlorophenyl)thiazole compounds are promising candidates for antimalarials.

Pectin-like Polysaccharide Extracted from the Leaves Caesalpinia pulcherrima is a Promising Antioxidant and Immunomodulator Agent

Abstract Studies have shown that Caesalpinia pulcherrima extracts promote antioxidant, healing, immunomodulating and antiparasitic activities and its polysaccharides can be used as functional food. In this sense, this work had as objective the isolation and characterization of a polysaccharide-like pectin, extracted from the C. pulcherrima leaves and its possible applications as an antioxidant and immunomodulator agent. The molecule was characterized by high performance liquid chromatography, fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. Its antioxidant potential was evaluated through the methods of phosphomolybdenum, ABTS radical scavenging [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid], DPPH (1,1-diphenyl-2-picrylhydrazyl) and nitric oxide radical. The immunostimulating effects of pectin were tested in splenocytes to evaluate its toxic, proliferative and cell activator and immunomodulatory potential. The polysaccharide obtained has structural characteristics similar to pectins. Pectin showed high in vitro antioxidant activity for ABTS radical scavenging, moderate activity for phosphomolybdenum and low activity for DPPH and nitric oxide. In vitro immunomodulation assays showed that pectin obtained did not promote a cytotoxic effect (viability > 90%). The increase in cytosolic ROS levels indicates a possible mechanism of cell activation without causing damage. Immunophenotyping showed that pectin increased a subpopulation of CD8+ T lymphocytes and monocytes. In addition, it promoted a mostly pro-inflammatory response confirmed by the production of cytokines IL-2, -4, -6, IFN-γ and TNF-α. These results reinforce the ethnopharmacological use of C. pulcherrima leaves and expand the use of this plant for future applications as herbal medicines.

Efeitos dos picnogenol® na doença aterosclerótica crônica / Effects of picnogenol® on chronic atherosclerosis

A doença aterosclerótica crônica (DAC) é uma condição bastante prevalente em nosso meio e uma das principais doenças cardiovasculares ligadas ao envelhecimento. Dentre as opções terapêuticas adjuvantes, o Picnogenol ®, extrato da casca do Pinus pinaster, tem sido alvo de estudo em decorrência de função antioxidante, anti-inflamatória e antiplaquetária. Este artigo é uma revisão narrativa, cujo objetivo é avaliar o uso do Picnogenol® como opção terapêutica da DAC. Os estudos incluídos foram pesquisados nas bases de dados: PubMed, Scielo, The Cochrane Library, Scopus e LILACS, sendo excluídos, considerando suas restrições para avaliação terapêutica, os relatos de caso e séries de caso com n ≤ 5. Como resultado, os estudos têm apontado vantagens do uso Picnogenol® no tratamento da DAC, assim como de outras doenças cardiovasculares, porém, o número de pesquisas ainda é pequeno (principalmente ensaios clínicos) e há importantes limitações de tamanho amostral, o que dificulta sua atual recomendação na prática clínica

Chronic atherosclerosis is a highly prevalent condition and one of the main cardiovascular diseases linked to the aging process. Among the adjuvant therapeutic options, Pycnogenol® (Pinus pinaster bark extract) has been studied because of its antioxidant, anti-inflammatory and antiplatelet functions. This article is a narrative review aimed at evaluating the use of Pycnogenol® as a therapeutic option in the treatment of chronic atherosclerosis. The studies included were obtained from the following databases: PubMed, Scielo, The Cochrane Library, Scopus and LILACS. Case reports and case series with n≤5 were excluded due to their restrictions for therapeutic evaluation. As a result, the studies have indicated advantages in the use of Pycnogenol® in the treatment of chronic atherosclerosis as well as other cardiovascular diseases. However, the number of studies is still small (particularly clinical trials), and there are important sample size limitations, which restricts its current recommendation in clinical practice

Impacts of Cytochrome P450 2D6 (CYP2D6) Genetic Polymorphism in Tamoxifen Therapy for Breast Cancer.

Tamoxifen (TMX) is the main drug used both in pre and postmenopausal women as adjuvant treatment for hormone receptor-positive breast cancer. An important barrier to the use of TMX is the development of drug resistance caused by molecular processes related to genetic and epigenetic mechanisms, such as the actions of cytochrome P450 2D6 (CYP2D6) polymorphisms and of its metabolites. The present study aimed to review recent findings related to the impact of CYP2D6 polymorphisms and how they can affect the results of TMX in breast cancer treatment. The keywords CYP2D6, tamoxifen, and breast cancer were searched in the PubMed, Scopus, The Cochrane Library, Scielo, and Bireme databases. Studies related to other types of neoplasms or based on other isoenzymes from cytochrome P450, but not on CYP2D6, were excluded. The impact of CYP2D6 polymorphisms in the TMX resistance mechanism remains unclear. The CYP2D6 gene seems to contribute to decreasing the efficacy of TMX, while the main mechanism responsible for therapy failure, morbidity, and mortality is the progression of the disease.

O tamoxifeno é a principal droga que pode ser utilizada como tratamento hormonal adjuvante em pacientes portadoras de câncer de mama receptor hormonal positivo tanto na pré- quanto na pós-menopausa. Uma das maiores barreiras em seu uso é o desenvolvimento de resistência medicamentosa causada por meio de processos moleculares relacionados a mecanismos genéticos e epigenéticos, como a ação dos polimorfismos do gene citocromo P450 2D6 (CYP2D6) e seus metabólitos. O presente estudo busca revisar as descobertas recentes acerca dos impactos dos polimorfismos do gene CYP2D6 e de como eles podem afetar os resultados do tamoxifeno na terapêutica do câncer de mama. As palavras-chave CYP2D6, tamoxifeno e câncer de mama foram buscadas nas bases de dados Pubmed, Scopus, The Cochrane Library, Scielo e Bireme. Estudos relacionados com outros tipos de câncer ou relacionados a outras isoenzimas do citocromo P450 que não o CYP2D6 foram excluídos. O impacto do polimorfismo do CYP2D6 nos mecanismos de resistência ao tamoxifeno permanecem controversos. O gene CYP2D6 parece reduzir a eficácia do TMX; entretanto, os principais fatores associados a falha terapêutica são morbimortalidade e a progressão da doença.