A novel interaction between the enzyme platelet-activating factor acetyl hydrolase (PAF-AH) and certain non-steroidal anti-inflammatory drugs (NSAIDs), such as sulindac, celecoxib, diclofenac and nimesulide, has been uncovered by this in-silico research. PAF-AH is known for its critical role in maintaining the fluidity and functionality of cell membranes by hydrolysing phospholipids and removing oxidized fatty acids. Since tumour microenvironments are largely marked by inflammation and oxidative stress, the discovery that these non-steroidal anti-inflammatory drugs can bind to the active pocket of PAF-AH. Suggests that they may be able to modulate its activity and thereby influence its role in cancer pathogenesis. Such modulation could lead to significant anti-tumour effects, including the reduction of inflammation, the inhibition of angiogenesis and the suppression of metastasis, particularly in cancers of the breast, colon, prostate, and lung. However, in certain con-texts, this interaction may cause the opposite effect, leading to cancer development. Therefore, this study is a gateway for the development of therapeutic strategies based on PAF-AH modulation and highlights the importance of the tumour microenvironment in the assessment of potential effects of NSAIDs. Furthermore, this finding may guide the selection of NSAIDs for the anti-inflammatory treatment of cancer patients, ruling out in-discriminate use of drugs that may promote neoplastic progression. This may also indicate the potential for repositioning specific NSAIDs within cancer treatment, thereby contributing to more precise and personalized therapeutic approaches.

The eugenol derivative, ethyl 4-(2-methoxy-4-(oxiran-2-ylmethyl)phenoxy)butanoate 1, with promising insecticidal capability was encapsulated in liposomal formulations of egg-phosphatidylcholine/cholesterol (Egg-PC:Ch) 70:30 and of 100% dioleoylphosphatidylglycerol (DOPG). Compound-loaded Egg-PC:Ch liposomes exhibit small hydrodynamic diameters (below 100 nm), high encapsulation efficiency (88.8% ± 2.7%), higher stability and a more efficient compound release, being chosen for assays in Sf9 insect cells. Compound 1 elicited a loss of cell viability up to 80% after 72h of incubation. Relevantly, encapsulation maintained the toxicity of compound 1 towards insect cells, while it lowered toxicity towards human cells, thus showing the selectivity of the system. Structure based inverted virtual screening was used to predict the most likely targets and molecular dynamics simulations and free energy calculations were used to demonstrate that this molecule can form a stable complex with insect odorant binding proteins and/or acetylcholinesterase.

Botanical biopesticides have emerged as sustainable and eco-friendly alternatives to synthetic pesticides, whose indiscriminate use leads to several drawbacks to human and environment health. The present study reports on the evaluation of the roots extract from Magonia pubescens, species from the Cerrado (Brazilian savannah), on the phytopathogenic fungi, Alternaria alternata, Botrytis cinerea, and Fusarium oxysporum. In addition, its insect antifeedant effect was assayed against Chrysodeixis chalcites. Thus, an in vitro test-assay was used to determine the fungicide potential (percentage growth inhibition, % GI) of the ethanolic extract of this plant species, whereas a leaf-disk bioassay on the 5^th instar larvae of C. chalcites was performed to evaluate the insecticide potential. The ethanolic extract was further fractionated by liquid-liquid extraction, using organic solvents of increasing polarity. The hexane/dichloromethane fraction exhibited a moderated potency, and similar to the ethanolic extract on the three assayed fungi (around % GI 30 at 1 mg/mL), whereas the n-butanol fraction showed a slight improvement of the fungicide effect against B. cinerea (% GI 39.18 at 1 mg/mL). Moreover, the etanolic extract exhibited a strong antifeedant activity, with a refusal rate (FR) higher than 90% in both choice and non-choice assays against C. chalcites, while the ethyl acetate and n-butanol fractions behaved as appetite suppressors. These results highlight M. pubescens as a promising source of biopesticides and deserve further investigations to optimize extraction procedures.