RESUMO
Isoxazoline is a 5-membered heterocycle present in the active compounds of many commercial veterinary anti-ectoparasitic products. The molecular target of isoxazolines is the inhibition of GABA-gated chloride channels in insects. These facts have inspired the use of the isoxazoline scaffold in the design of novel insecticide compounds. The main strategies used for isoxazoline synthesis are either the 1,3-dipolar cycloaddition between a nitrile oxide and an alkene or the reaction between hydroxylamine and an α,ß-unsaturated carbonyl compound. This review highlights the utilization of isoxazoline as insecticide: its mode of action, its commercial preparations and its consideration in the design of novel insecticides. Similarity analyses were performed with 235 isoxazoline derivatives in three different cheminformatic approaches - chemical property correlations, similarity network and compound clustering. The cheminformatic methodologies are interesting tools to use in evaluating the similarity between commercial isoxazolines and to clarify the main features explored within their derivatives.
Assuntos
Desenvolvimento de Medicamentos , Insetos/efeitos dos fármacos , Inseticidas/farmacologia , Isoxazóis/farmacologia , Animais , Inseticidas/síntese química , Inseticidas/química , Isoxazóis/síntese química , Isoxazóis/química , Estrutura Molecular , Receptores de GABA/metabolismoRESUMO
ETHNOPHARMACOLOGY RELEVANCE: The plants of Amaryllidaceae family, such as Amaryllis belladonna L., have been used as herbal remedies for thousands of years to address various disorders, including diseases that might today be identified as cancer. AIM OF THE STUDY: The objective of this work was to evaluate the potential of three Amaryllidaceae alkaloids against four cancer cell lines. MATERIAL AND METHODS: The alkaloids lycorine, 1-O-acetylcaranine, and montanine were evaluated in vitro against colon adenocarcinoma cell line (HCT-116) and breast carcinoma cell lines (MCF-7, MDAMB231, and Hs578T). Computational experiments (target prediction and molecular docking) were conducted to gain a deeper comprehension of possible interactions between these alkaloids and potential targets associated with these tumor cells. RESULTS: Montanine presented the best results against HCT-116, MDAMB231, and Hs578T cell lines, while lycorine was the most active against MCF-7. In alignment with the target prediction outcomes and existing literature, four potential targets were chosen for the molecular docking analysis: CDK8, EGFR, ER-alpha, and dCK. The docking scores revealed two potential targets for the alkaloids with scores similar to co-crystallized inhibitors and substrates: CDK8 and dCK. A visual analysis of the optimal docked configurations indicates that the alkaloids may interact with some key residues in contrast to the other docked compounds. This observation implies their potential to bind effectively to both targets. CONCLUSIONS: In vitro and in silico results corroborate with data literature suggesting the Amaryllidaceae alkaloids as interesting molecules with antitumoral properties, especially montanine, which showed the best in vitro results against colorectal and breast carcinoma. More studies are necessary to confirm the targets and pharmaceutical potential of montanine against these cancer cell lines.
Assuntos
Alcaloides de Amaryllidaceae , Antineoplásicos Fitogênicos , Simulação de Acoplamento Molecular , Humanos , Alcaloides de Amaryllidaceae/farmacologia , Alcaloides de Amaryllidaceae/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Células MCF-7 , Amaryllidaceae/química , Células HCT116 , Simulação por Computador , Fenantridinas/farmacologia , Fenantridinas/química , IsoquinolinasRESUMO
ABSTRACT: Toxoplasmosis is a zoonosis caused by Toxoplasma gondii, which can be acquired by oral contact and may cause severe health problems especially for pregnant (congenital toxoplasmosis) and immunocompromised patients. This study aimed to verify the diagnostic significance of hematological parameters and C-reactive protein (CRP) for toxoplasmosis acute detection. A case-control study was carried out between December 2017 and May 2018, in samples of convenience independent of age and sex. The case group was formed by 25 patients with positive anti-Toxoplasma gondii IgG/IgM antibody and the control group was formed by 21 patients with non-positive anti-Toxoplasma gondii IgG/IgM antibody. The results of the hematological parameters and CRP were analyzed in these patients. The patients with Toxoplasma gondii IgM antibody reagent showed higher lymphocytes counting and lower neutrophils counting than the control group. C-reactive protein levels were not different between the groups case and control. ROC curve analysis highlighted that the cut-off value of > 32.00% for lymphocytes and < 57.50% for neutrophils were able to produce specificity higher than 90% for IgM antibody detection. The Naïve Bayes classifier was considered suitable (AUC ≈ 0.700) to separate both groups according to their white cell counting. Changes in lymphocytes and neutrophils may be useful parameters for toxoplasmosis identification and may be used as a tool in the complementary diagnosis of toxoplasmosis.