The use of chemicals to boost food production increases as human consumption also increases. The insectidal, nematicidal and acaricidal chemical carbofuran (CAF), is among the highly toxic carbamate pesticide used today. Alongside, copper oxide nanoparticles (CuO) are also used as pesticides due to their broad-spectrum antimicrobial activity. The overuse of these pesticides may lead to leaching into the aquatic environments and could potentially cause adverse effects to aquatic animals. The aim of this study is to assess the effects of carbofuran and copper oxide nanoparticles into the cardiovascular system of zebrafish and unveil the mechanism behind them. We found that a combination of copper oxide nanoparticle and carbofuran increases cardiac edema in zebrafish larvae and disturbs cardiac rhythm of zebrafish. Furthermore, molecular docking data show that carbofuran inhibits acetylcholinesterase (AChE) activity in silico, thus leading to impair cardiac rhythms. Overall, our data suggest that copper oxide nanoparticle and carbofuran combinations work synergistically to enhance toxicity on the cardiovascular performance of zebrafish larvae.
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The ongoing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has been proven to be more severe than the previous coronavirus outbreaks due to the virus’ high transmissibility. With the emergence of new variants, this global phenomenon took on a more dramatic turn with many countries recently experiencing higher surges of confirmed cases and deaths. On top of this, the inadequacy of effective treatment options for COVID-19 aggravated the problem. As a way to address the unavailability of target-specific viral therapeutics, computational strategies have been employed to hasten and systematize the search. The objective of this review is to provide initial data highlighting the utility of polyphenols as potential prophylaxis or treatment for COVID-19. In particular, presented here are virtually screened polyphenolic compounds which showed potential as either antagonists to viral entry and host cell recognition through binding with various receptor-binding regions of SARS-CoV-2 spike protein or as inhibitors of viral replication and post-translational modifications through binding with essential SARS-CoV-2 non-structural proteins.
Tuberculosis (TB) and cancer are among the maladies with high morbidity and mortality rates to date. This prompted the utilization of natural products in the discovery and development of new anti-TB and anticancer derivatives. In this study, we explored the antitubercular and antiproliferative activities of extracts and tetrahydrobisbenzylisoquinoline alkaloids tetrandrine (1) and limacusine (2) from the Philippine medicinal plant Phaeanthus ophthalmicus. Antitubercular evaluation using colorimetric MABA (microplate Alamar blue assay) assays revealed antitubercular activities of the extracts and fractions [minimum inhibitory concentration (MIC) = 15.6 to < 64 μg/mL]. Among the two isolated alkaloids, limacusine (2) exhibited inhibitory activity against Mycobacterium tuberculosis (MIC = 42.6 μg/ml). In addition, CellTiter-Blue cell viability assay showed antiproliferative activity for limacusine (2) against K-562. Both tetrahydrobisbenzylisoquinoline alkaloids exhibited cytotoxicity on HeLa cells. To probe the binding mechanisms of 1 and 2 against putative protein targets, molecular docking simulations were carried out. Limacusine (2) showed high binding propensities to mycobacterial enzymes ATP-dependent murE ligase and enoyl acyl carrier protein reductase, thus illustrating possibilities of cell wall and mycolic biosynthesis inhibitory mechanisms, respectively. High binding affinity was also observed in 2 vs. FLT3, a protein target implicated in myeloid leukemia cell proliferation. Additionally, the limacusine-InhA and limacusine-FLT3 complexes were found to be dynamically stable as per molecular dynamics (MD) simulations. The results of in vitro
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