Alternative treatment modalities are being sought after reports of rising anthelminthic medication µresistance and their combination. This study looked at the helminthicidal and inhibitory effects of P. nitida extract on a few targets for metabolic enzymes in Fasciola gigantica. A complete Randomized Design (CRD) of 13 treatments duplicated three times with six adult F. gigantica in each replicate was used. Group A had no treatment (experimental control) and received no extracts at all. Mebendazole (Mevadex), 50 µg/mL, was administered to Group B-E as the standard control. The experimental groups F–I and J–M received treatments with water and methanol extracts of P. nitida leaf, respectively. Percentage mortality, motility, and impact of the extracts on some metabolic enzymes were assayed. At the third hour of exposure, all test groups' F. gigantica mortality levels significantly increased (p < 0.05) compared to the control. At 600 µg/mL concentration, the methanol fraction had a greatest death rate of 94.4% (n = 17) in 3 hours. In comparison to the control, there was a substantial drop in glycolytic enzymes (p < 0.05). Hexokinase (1.92 ± 0.09 U/g at 150 µg/ml), Pyruvate kinase (5.88 ± 0.91 U/g at 600 µg/ml), and Glucose Phosphate Isomerase (4.22 ± 0.68 U/g at 600 µg/ml) all showed greater effects in the aqueous fraction. The trend was independent of concentration. The decrease in the glycolytic enzyme levels suggests that P. nitida extract exhibited helminthicidal property by decreasing the liver fluke metabolic rate, offering a target for pharmacological intervention.

Spinal muscular atrophy is a neuromuscular disorder caused by mutations in both copies of the survival motor neuron gene 1 (SMN1) which lead to reduction in the production of the SMN protein. Currently, there are several therapies that have been approved for SMA. Nonetheless, an urgent need to develop a new therapeutic approach is still of a high value as well as a powerful biomarker capable of assessing the effectiveness of SMA treatment, as a universally accepted one still has not been identified. This study aimed at investigating the quantity of gems in cell nuclei as a potential biomarker for SMA. Fibroblast cell cultures obtained from a patient with SMA type II and from a healthy individual were used to gain insight whether the number of gems in cell nuclei varies based on their SMN genotype and whether its increase is associated with therapeutic response. We discovered a remarkable difference in the number of gems in the nuclei of cells with different genotypes, specifically when counting gems per 100 nuclei. SMA fibroblasts were further treated with antisense oligonucleotides previously proved to have beneficial effects in correcting the abnormal splicing of SMN2 exon 7. We observed a significant increase in the number of gems in the treated cells compared to the intact SMA cells. The obtained results correlate significantly with the increase in full-length SMN transcripts level. Based on our findings, it is evident that the number of gems can be considered as a reliable biomarker for SMA drugs development.

Melanoma is an aggressive type of skin cancer, with the number of cases expected to increase in the future. The available treatments show low efficiency highlighting the need to develop new therapies to increase the survival of the patients. Beta-blockers, drugs already known and used for heart conditions; have shown anti-cancer properties and potential to be valuable in conjugation with chemotherapy. This study aimed to evaluate, in vitro, their potential for cancer treatment. A375 cells (melanoma cell line) were exposed to non-selective blockers (carvedilol and propranolol), β1 selective blockers (atenolol and metoprolol), and antineoplastics drugs (cisplatin and 5- fluorouracil), and viability assessed at 3 timepoints. Selective beta-1 blockers had no significant effects on cell viability. However, the other tested pharmaceuticals affected cell viability allowing the determination of median lethal concentrations (LC50) at 72h and a toxicity ranking: cisplatin (2.46 (1.87 – 3.38), 5-fluorouracil (4.77 (4.48 – 5.07)), carvedilol (16.91 (15.47 - 18.99)) and propranolol (58.03 (57.08 - 59.11)). Carvedilol and cisplatin were, respectively, the most toxic beta-blocker and antineoplastic. Following these results, a combined exposure of beta-blockers and antineoplastics was performed: cisplatin with metoprolol, propranolol, and carvedilol and also paired both non-selective beta-blockers. The results so far support the potential use of non-selective β-blockers as adjuvants of chemotherapy as a melanoma treatment.

Respiratory syncytial virus infection (RSV) is currently a widespread disease worldwide, which is severe in the elderly and young children, leading to severe complications and even death. No specific etiotropic therapy currently exists. Several groups of researchers around the world are actively developing antiviral agents against MS infection, but none of them is yet suitable for widespread use in clinical practice. Diffractic acid is one of the major secondary metabolites of many lichens and belongs to the class of depsides. There are few studies devoted to its biological activity. This compound is known to have moderate antibacterial and insecticidal properties, as well as antiulcer and hepatoprotective activity. Our group developed an isolation technique and isolated diffractic acid from a mixture of lichens of the genus Usnea. Tests on the ability to inhibit RSV reproduction in vitro showed that diffractaic acid has significant antiviral activity against RSV: EC₅₀ = 4.8 μM, CC₅₀ = 221.9 μM, SI = 46.

To address the challenge of mitigating the adverse effects and drug resistance associated with Pt(II) chemotherapeutic compounds, significant efforts have been devoted to designing metal-based drugs with diverse anticancer mechanisms. Exploring alternative organometallic complexes, such as those incorporating silver, is an interesting approach in the pursuit of more effective and safe treatments.

This study aims to develop a new family of silver(I) complexes with nitrogen donor ligands that exhibit antitumor properties, and to determine the mechanism by which these compounds induce cell death, such as the generation of reactive oxygen species (ROS).

A novel family of eight silver complexes was synthesized using a newly developed imine, (E)-N-(3,5-bis(trifluoromethyl)benzyl)-1-(4-(piperidin-1-yl)phenyl)methanamine, which was formed by condensing two pharmacophores. This study employed two tumor cell lines: cervical cancer (HeLa) and hepatocellular carcinoma (Hep-G2). To assess their antitumor potential, MTT assays were conducted. Additionally, the generation of ROS in HeLa cells was measured as possible mechanism of action to understand their effects.

The results indicate that, with one exception, new compounds exhibit activity against both assayed lines. Higher cytotoxic activity of the compounds was observed against the HeLa cell line, except for compound ZAG-14.2, which showed greater efficacy against Hep-G2. Regarding the production of ROS, it was observed that exposure to the compounds increased ROS levels in HeLa cells compared to control cells.

The potential of these new complexes as anticancer drugs is evident through their significant cytotoxic activity in both cell lines. Further studies are needed to fully understand their mechanism of action.

Despite the efforts made to stop the tuberculosis epidemic, it still remains one of the leading causes of death from an infectious disease. Previous work in the group uncovered a new family of amides which showed promising activities against Mycobacterium tuberculosis. A closer look at the literature showed that these compounds are structurally related to the DNB family of inhibitors of DprE1, an essential epimerase for the formation of a vital precursor of the arabinogalactan biosynthesis, one of the components of the mycobacterial cell wall. Following those results, we decided to study a wide range of substituted amides and determine their activity, focusing on unexplored structures related to the dinitrobenzamides (DNB) found in the literature. To synthesize our library of compounds we started from 3,5-dinitrobenzoic acid to form the nitroaromatic core that is characteristic of the DNB’s, to which we then added linear or cyclic amine moieties Additionally, the impact of terminal aromatic moieties was also assessed for some derivatives, via an ether, ester or amide bond. In order to obtain the desired derivatives, multiple synthetic approaches were used, mainly focused in nucleophilic addition/elimination reactions, S_N2 reactions and Mitsunobu reactions. The most interesting compounds exhibited activities in the 100-200nM range, and we’re currently developing an extended family of compounds based in those structures. Additionally, computational studies were performed aimed at further understanding their interactions with DprE1 and comparing it to known DNB’s.

Black soldier fly (BSF) larvae biomass can be viewed as an innovative source of compounds with high aggregate value and marketing potential due to the sustainable organic matter bioconversion process used as a substrate for its development. The larvae lipid fraction seems particularly promising as a source of added-value lipids for the pharmaceutical and cosmetic industries, mainly due to its blend of mono and polyunsaturated fatty acids (FA). Dysfunctions in the cutaneous barrier are behind many pathologies, resulting in clinical manifestations such as inflammatory processes. Some of these disorders are related to alterations or depletion of the SC lipidic matrix. The lipid fraction of BSF larvae biomass can be foreseen to provide barrier recovery and emollient ingredients for topical formulations due to good biocompatibility that is expected for this raw material, since FA are critical in skin barrier function. Different methods of extraction were then tested and, in general, the lauric acid (C12:0) was prevalent in all extractions, followed by the palmitic (C16:0), linoleic (C18:2), and oleic (C18:1n-9) acids. Nanotechnology has provided promising and advanced tools for the delivery of drugs and actives for topical application in the context of skin diseases with barrier impairment. Lipid-based, polymeric and hybrid nanoparticles have been explored to load glucocorticoids for topical application in the management of these skin conditions. Moreover, lipid-based and polymeric nanosystems have been explored to provide ceramides by topical application, reinforcing the skin barrier. In this context, multifunctional nano-based formulations joining FA, ceramides and glucocorticoids may bode well for the future of managing skin diseases with barrier impairment.

Tuberculosis (TB) remains a formidable global health challenge, with an annual reporting of approximately 10 million new cases. The escalating concern revolves around multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), which present barriers to effective disease control due to their resistance to both first-line and second-line drugs. One of the most promising new targets for TB treatment is the DprE1-DprE2 complex, with ongoing discoveries of novel inhibitors.

In prior unrelated research, our group showed that while studying benzoic acid derivatives, the nitro-substituted analogues exhibited interesting activity against Mycobacterium tuberculosis (Mtb). This motivated us to synthesize analogous amide derivatives, and our findings show substantial antimycobacterial activity, on par or even greater than known TB drugs.

Dinitrobenzamides represent a class of established DprE1 inhibitors, but its alkyl derivatives, akin to the compounds under discussion, were completely overlooked in available literature. Building upon our prior insights, which indicates that 8-carbon atom alkyl derivatives yielded the most potent compounds, we synthesized a series of amide derivatives and, indeed, our study shows 8-carbon atom alkyl amides amongst the most efficacious. This study extensively explores a series of nitro-substituted benzoic amide alkyl derivatives, elucidating the influence of the number and position of nitro-groups on their antitubercular activity. Moreover, we conducted supplementary biological and computational assays to assess the potential targeting of DprE1 by these compounds, as well as their efficacy in an infection model, all of which will be presented and discussed herein.

The combination of 3D printing and shape-memory materials has provided new insights into the design and manufacture of customized medicines by enabling the unique design of drug delivery systems while allowing them to retain specific predefined shape until triggered by external stimuli such as body temperature or gastrointestinal pH. In this study, we investigated the feasibility of utilizing fused deposition modeling (FDM) 3D printing to fabricate a shape-memory polymer-based drug delivery platform specifically designed in helical structure. This platform can be compressed and temporarily fixed into tablet-like shape for patients to easily swallow before reverting back to its original shape in stomach. Furthermore, this study investigated the influence of 3D model design parameters (e.g., helix diameter, height, turns) and process parameters (e.g., layer height, nozzle temperature, programming temperature for shape fixation) on shape fidelity and shape memory behavior of the platform. The findings demonstrated that the platform with helix shape was most effectively transformed into a tablet-like shape when the programming temperature was close to the glass transition temperature (T_g) of printing filament. However, when the temperature exceeded T_g, the platform became too soft, thus resulting in 3D structure distortion and decreasing in shape fidelity. Additionally, shape memory testing showed that the developed platforms were able to revert to their original shape with a recovery ratio of 40-50% in 30 minutes when subjected to 0.1N hydrochloric acid at 37 °C. These findings provide crucial insights for future research on utilizing this platform for stomach-specific drug delivery, particularly in gastroretentive approaches.

Finding treatments to neurodegenerative diseases such as Alzheimer’s disease AD is one of the biggest challenges for scientists working in the medicinal field, due to the fact that these pathologies are complex, difficult to prevent, and multifactorial. Indeed, AD progression involves different proteins and enzymes including acetylcholine esterase AChE. There is no cure for AD, but there is symptomatic treatments in which the AChE inhibitors takes the major place, that is what made AChE the main drug target in the conception of new anti-AD agents.

Our interest was sought to a specific class of small molecules containing the enaminocarboxamide scaffold combining both enaminone and primary amide moieties. A docking simulation was performed to explore the binding mode of studied compounds and the active site of AChE (PDB: 1ACJ) using Schrödinger suite for the docking calculation and Chimera for the 3D visualization. The studied derivatives showed a great stability inside the cavity of AChE with a docking score included between -9.685 and -8.726 kcal.mol^-1. This stability was supported by different interactions with the key residues of the active site including hydrogen bonds with His440, a water bridge with Trp84 as well as pi-pi stacking with Trp84 and Phe330. Additional interactions were perceived with Ser200 and Tyr121 residues. The promising results of docking simulation prompted us to complete the in silico investigation by predicting drug-likeness and ADME properties of the studied compounds using MolSoft and SwissADME as accurate predictive tools.