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The SARS-CoV-2 mutation and the limitation of the approved drug against COVID-19 are still a challenge in many country healthcare systems and need to be affronted despite the set of vaccines to prevent this viral infection. To contribute to the identification of new antiviral agents, the present study focused on natural products from an edible fruit with potential inhibitory effects against the SARS-CoV-2 main protease (M pro ). First, LC-ESIMS analysis of Platonia insignis fruits was performed and showed the presence of biflavonoids and benzophenones in the seed and pulp, respectively. Then, maceration and chromatographic purification led to the identification of two triglycerides (1 and 2) alongside chamaejasmine (3) and volkensiflavone (4) from the seed and isogarcinol (5) and cycloxanthochymol (6), from the pulp. Compounds 1-6 after evaluating their inhibitory against M pro , displayed from no to significant activity. Compound 5 was the most potent with an IC 50 value of 0.72 μM and was more active than the positive control, Ebselen (IC 50 of 3.4 μM). It displayed weak and no cytotoxicity against THP-1 (CC 50 of 116.2 μM) and Vero cell lines, respectively. Other active compounds showed no cytotoxicity against THP-1. and Vero cell lines. Molecular docking studies revealed interactions in the catalytic pocket between compound 5 and amino acid residues that composed the catalytic dyads (His 41 and Cyst 145)., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Organic chemicals identified in raw landfill leachate (LL) and their transformation products (TPs), formed during Fenton treatment, were analyzed for chemical safety following REACH guidelines. The raw LL was located in the metropolitan region of Campina Grande, in northeast Brazil. We elucidated 197 unique chemical structures, including 154 compounds that were present in raw LL and 82 compounds that were detected in the treated LL, totaling 39 persistent compounds and 43 TPs. In silico models were developed to identify and prioritize the potential level of hazard/risk these compounds pose to the environment and society. The models revealed that the Fenton process improved the biodegradability of TPs. Still, a slight increase in ecotoxicological effects was observed among the compounds in treated LL compared with those present in raw LL. No differences were observed for aryl hydrocarbon receptor (AhR) and antioxidant response element (ARE) mutagenicity. Similar behavior among both raw and treated LL samples was observed for biodegradability; Tetrahymena pyriformis, Daphnia magna, Pimephales promelas and ARE, AhR, and Ames mutagenicity. Overall, our results suggest that raw and treated LL samples have similar activity profiles for all endpoints other than biodegradability., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Persistent organic products are compounds used for various purposes, such as personal care products, surfactants, colorants, industrial additives, food, pesticides and pharmaceuticals. These substances are constantly introduced into the environment and many of these pollutants are difficult to degrade. Toxic compounds classified as MoA 1 (Mode of Action 1) are low toxicity compounds that comprise nonreactive chemicals. In silico methods such as Quantitative Structure-Activity Relationships (QSARs) have been used to develop important models for prediction in several areas of science, as well as aquatic toxicity studies. The aim of the present study was to build a QSAR model-based set of theoretical Volsurf molecular descriptors using the fish acute toxicity values of compounds defined as MoA 1 to identify the molecular properties related to this mechanism. The selected Partial Least Squares (PLS) results based on the values of cross-validation coefficients of determination (Q cv 2 ) show the following values: Q cv 2 = 0.793, coefficient of determination (R 2 ) = 0.823, explained variance in external prediction (Q ext 2 ) = 0.87. From the selected descriptors, not only the hydrophobicity is related to the toxicity as already mentioned in previously published studies but other physicochemical properties combined contribute to the activity of these compounds. The symmetric distribution of the hydrophobic moieties in the structure of the compounds as well as the shape, as branched chains, are important features that are related to the toxicity. This information from the model can be useful in predicting so as to minimize the toxicity of organic compounds., (Copyright © 2018. Published by Elsevier Inc.)

The anti-hyperalgesic effect of the complex containing α-terpineol (αTPN) and β-cyclodextrin (βCD) was analyzed in a non-inflammatory chronic muscle pain model, as well as its mechanism of action through docking study for a possible interaction with receptors. The αTPN-βCD complex was prepared and characterized through the thermogravimetry/derivate thermogravimetry (TG/DTG), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The model of chronic muscle pain was induced by two injections of pH 4.0 saline (20 μl) into the left gastrocnemius 5 days apart. After confirming hyperalgesia, male mice were treated with αTPN-βCD (25, 50 or 100 mg/kg; p.o.) or vehicle (saline 0.9%, p.o.) daily for 10 days. 1 h after the mechanical hyperalgesia, motor performance was evaluated. In addition, the systemic administration of naloxone and ondansetron tested the analgesic effect on the active opioid and serotonin receptors, respectively. The characterization tests indicated that αTPN was efficiently incorporated into βCD. The oral treatment with αTPN-βCD, at all doses tested, produced a significant (p < 0.001) decrease in the mechanical hyperalgesia, without causing any alteration in the force and in motor performance. This analgesic effect was reversed by the systemic administration of naloxone or ondansetron. These findings are corroborated by the docking study described in the present study, which verified a possible interaction of αTPN-βCD with opioid (MU, Kappa, Delta) and 5-HT receptors. Thus, it can be concluded that αTPN-βCD reduced the hyperalgesia followed by the chronic muscle pain model, probably evoked by the descending inhibitory pain system, specifically by opioid and serotoninergic receptors., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aims: The present study evaluated the carvacrol (CARV) effect on hyperalgesia and nociception induced by sarcoma 180 (S180) in mice., Main Methods: Carvacrol treatment (12.5-50mg/kgs.c.) once daily for 15days was started 24h after injection of the sarcoma cells in the hind paw (s.c.). Mice were evaluated for mechanical sensitivity (von Frey), spontaneous and palpation-induced nociception, limb use and tumor growth on alternate days. CARV effects on the central nervous system were evaluated through immunofluorescence for Fos protein. Molecular docking studies also were performed to evaluate intermolecular interactions of the carvacrol and muscimol, as ligands of interleukin-10 and GABAA receptors., Key Findings: CARV was able to significantly reduce mechanical hyperalgesia and spontaneous and palpation-induced nociception, improve use paw, decrease the number of positively marked neurons in lumbar spinal cord and activate periaqueductal gray, nucleus raphe magnus and locus coeruleus. CARV also caused significant decreased tumor growth. Docking studies showed favorable interaction overlay of the CARV with IL-10 and GABAA., Significance: Together, these results demonstrated that CARV may be an interesting option for the development of new analgesic drugs for the management of cancer pain., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Feed-forward neural networks (FFNNs) were used to predict the skeletal type of molecules belonging to six classes of terpenoids. A database that contains the 13C NMR spectra of about 5000 compounds was used to train the FFNNs. An efficient representation of the spectra was designed and the constitution of the best FFNN input vector format resorted from an heuristic approach. The latter was derived from general considerations on terpenoid structures.