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1.
Mar Drugs ; 21(8)2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37623715

RESUMO

Chagas disease, sleeping sickness and malaria are infectious diseases caused by protozoan parasites that kill millions of people worldwide. Here, we performed in vitro assays of Pa-MAP, Pa-MAP1.9, and Pa-MAP2 synthetic polyalanine peptides derived from the polar fish Pleuronectes americanus toward Trypanosoma cruzi, T. brucei gambiense and Plasmodium falciparum activities. We demonstrated that the peptides Pa-MAP1.9 and Pa-MAP2 were effective to inhibit T. brucei growth. In addition, structural analyses using molecular dynamics (MD) studies showed that Pa-MAP2 penetrates deeper into the membrane and interacts more with phospholipids than Pa-MAP1.9, corroborating the previous in vitro results showing that Pa-MAP1.9 acts within the cell, while Pa-MAP2 acts via membrane lysis. In conclusion, polyalanine Pa-MAP1.9 and Pa-MAP2 presented activity against bloodstream forms of T. b. gambiense, thus encouraging further studies on the application of these peptides as a treatment for sleeping sickness.


Assuntos
Linguado , Tripanossomíase Africana , Animais , Peptídeos/farmacologia , Morte Celular , Peixes
2.
Brain Sci ; 14(1)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38248286

RESUMO

Epilepsy represents a condition in which abnormal neuronal discharges or the hyperexcitability of neurons occur with synchronicity, presenting a significant public health challenge. Prognostic factors, such as etiology, electroencephalogram (EEG) abnormalities, the type and number of seizures before treatment, as well as the initial unsatisfactory effects of medications, are important considerations. Although there are several third-generation antiepileptic drugs currently available, their multiple side effects can negatively affect patient quality of life. The inheritance and etiology of epilepsy are complex, involving multiple underlying genetic and epigenetic mechanisms. Different neurotransmitters play crucial roles in maintaining the normal physiology of different neurons. Dysregulations in neurotransmission, due to abnormal transmitter levels or changes in their receptors, can result in seizures. In this review, we address the roles played by various neurotransmitters and their receptors in the pathophysiology of epilepsy. Furthermore, we extensively explore the neurological mechanisms involved in the development and progression of epilepsy, along with its risk factors. Furthermore, we highlight the new therapeutic targets, along with pharmacological and non-pharmacological strategies currently employed in the treatment of epileptic syndromes, including drug interventions employed in clinical trials related to epilepsy.

3.
Pharmaceuticals (Basel) ; 15(6)2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35745643

RESUMO

Nature presents a wide range of biomolecules with pharmacological potential, including venomous animal proteins. Among the protein components from snake venoms, phospholipases (PLA2) are of great importance for the development of new anticancer compounds. Thus, we aimed to evaluate the PLA2 anticancer properties from Bothrops moojeni venom. The crude venom was purified through three chromatographic steps, monitored by enzymatic activity and SDS-PAGE (12%). The purified PLA2 denominated BmPLA2 had its molecular mass and N-terminal sequence identified by mass spectrometry and Edman degradation, respectively. BmPLA2 was assayed against human epithelial colorectal adenocarcinoma cells (Caco-2), human rhabdomyosarcoma cells (RD) and mucoepidermoid carcinoma of the lung (NCI-H292), using human fibroblast cells (MRC-5) and microglia cells (BV-2) as a cytotoxicity control. BmPLA2 presented 13,836 Da and a 24 amino acid-residue homologue with snake PLA2, which showed a 90% similarity with other Bothrops moojeni PLA2. BmPLA2 displayed an IC50 of 0.6 µM against Caco-2, and demonstrated a selectivity index of 1.85 (compared to MRC-5) and 6.33 (compared to BV-2), supporting its selectivity for cancer cells. In conclusion, we describe a new acidic phospholipase, which showed antitumor activity and is a potential candidate in the development of new biotechnological tools.

4.
Sci Total Environ ; 705: 135568, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31846817

RESUMO

Emerging contaminants are increasingly present in the environment, and their appearance on both the environment and health of living beings are still poorly understood by society. Conventional sewage treatment facilities that are under validity and were designed years ago are not developed to remove pharmaceutical compounds, their main focus is organic and bacteriological removal. Pharmaceutical residues are associated directly with quantitative production aspects as well as inadequate waste management policies. Persistent classes of emerging compounds such as xenobiotics present molecules whose physicochemical properties such as small molecular size, ionizability, water solubility, lipophilicity, polarity and volatility make degradability, identification and quantification of these complex compounds difficult. Based on research results showing that there is a possibility of risk to human and environmental health the presence of these compounds in the environment this article aimed to review the main pharmaceutical and xenobiotic residues present in the environment, as well as to present the most common methodologies used. The most commonly used analytical methods for identifying these compounds were HPLC and Gas Chromatography coupled with mass spectrometry with potential for characterize complex substances in the environment with low concentrations. An alternative and low-cost technology for emerging compound treatment demonstrated in the literature with a satisfactory performance for several types of sewage such as domestic sewage, wastewater and agroindustrial, was the Wetlands Constructed. The study was able to identify the main compounds that are being found in the environment and identify the most used analytical methods to identify and quantify these compounds, bringing some alternatives combining technologies for the treatment of compounds. Environmental contamination is eminent, since the production of emerging compounds aims to increase along with technological development. This demonstrates the need to explore and aggregate sewage treatment technologies to reduce or prevent the deposition of these compounds into the environment.


Assuntos
Purificação da Água , Monitoramento Ambiental , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Preparações Farmacêuticas , Esgotos , Águas Residuárias , Poluentes Químicos da Água , Xenobióticos
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