Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection continues to be a global health problem. Despite the current implementation of COVID‐19 vaccination schedules, identifying effective antiviral drug treatments for this disease continues to be a priority. A recent study showed that masitinib (MST), a tyrosine kinase inhibitor, blocks the proteolytic activity of SARS‐CoV‐2 main protease (M^pro). Although MST is a potential candidate for COVID‐19 treatment, a comprehensive analysis of its interaction with M^pro has not been done. In this work, we performed molecular dynamics simulations of the MST‐M^pro complex crystal structure. The effect of the protonation states of M^pro H163 residue and MST titratable groups were studied. Furthermore, we identified the MST substituents and M^pro mutations that affect the stability of the complex. Our results provide valuable insights into the design of new MST analogs as potential treatments for COVID‐19.

In this research work, a series of 16 quinazoline derivatives bearing ibuprofen and an amino acid were designed as inhibitors of epidermal growth factor receptor tyrosine kinase domain (EGFR‐TKD) and cyclooxygenase‐2 (COX‐2) with the intention of presenting dual action in their biological behavior. The designed compounds were synthesized and assessed for cytotoxicity on epithelial cancer cells lines (AGS, A‐431, MCF‐7, MDA‐MB‐231) and epithelial non‐tumorigenic cell line (HaCaT). From this evaluation, derivative 6 was observed to exhibit higher cytotoxic potency (IC₅₀) than gefitinib (reference drug) on three cancer cell lines (0.034 μM in A‐431, 2.67 μM in MCF‐7, and 3.64 μM in AGS) without showing activity on the non‐tumorigenic cell line (>100 μM). Furthermore, assessment of EGFR‐TKD inhibition by 6 showed a discreet difference compared to gefitinib. Additionally, 6 was used to conduct an in vivo anti‐inflammatory assay using the 12‐O‐tetradecanoylphorbol‐3‐acetate (TPA) method, and it was shown to be 5 times more potent than ibuprofen. Molecular dynamics studies of EGFR‐TKD revealed interactions between compound 6 and M793. On the other hand, one significant interaction was observed for COX‐2, involving S531. The RMSD graph indicated that the ligand remained stable in 50 ns.

Parkinson's disease (PD) is a progressive neurodegenerative disorder in which dopaminergic dysfunction is associated with oxidative stress, chronic neuroinflammation, and endoplasmic reticulum (ER)-stress-related signaling. ER-resident neurotrophic factors, cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF), have emerged as potential modulators of neuronal stress responses. Silybin, a flavonolignan derived from S. marianum, has antioxidant, anti-inflammatory, and neuroprotective effects in experimental PD models, although the molecular pathways underlying these effects remain incompletely defined. In this study, we evaluated whether silybin was associated with changes in CDNF/MANF levels, unfolded protein response-related markers, inflammatory mediators, and antioxidant enzyme activities in a subchronic MPTP mouse model. Silybin improved survival, reduced motor impairment, and partially preserved tyrosine hydroxylase content in the nigrostriatal pathway. Also, silybin selectively increased CDNF levels, whereas MANF remained unchanged. In parallel, silybin modulated PERK/eIF2α/ATF4- and IRE1α/XBP1-associated markers, lowered total NF-κB p65 and pro-inflammatory cytokine levels, and normalized several endogenous antioxidant enzyme activities. Correlation analyses identified CDNF as a prominent correlate of the protective phenotype, and in silico docking and molecular dynamics analyses further suggested that silybin may interact with PERK and IRE1α domains, providing a structural hypothesis compatible with the experimental findings. Overall, these results indicate that silybin modulates convergent changes in stress-, inflammatory-, and redox-related pathways in the MPTP model, together with selective CDNF upregulation and improved behavioral outcomes.

Novel pharmacological approaches advocate developing multitarget drugs, that is, molecules capable of simultaneously acting on two or more pharmacological targets to produce synergistic effects from a single compound in each disease. This strategy may help reduce required doses and prevent drug–drug interactions typically associated with polypharmacy. Coumarins are natural products with diverse pharmacological activities, including antioxidant, anti-inflammatory, anticancer, neuroprotective, cardioprotective, and antithrombotic effects. The pleiotropic actions of these molecules suggest that modifying the coumarin structure could yield new multi-target antiplatelet agents with greater efficacy and safety than those currently available in clinical practice. In this work, we began with a theoretical approach using molecular docking and designed three coumarins that simultaneously inhibited platelet aggregation induced by epinephrine, collagen, and ADP. Experimentally, we evaluated the structure activity relationship of three coumarins: (A) 6,7-dimethoxy-3-(1H-pyrrol-1-yl)-2H-chromen-2-one, (B) 7,8-dimethoxy-3-(1H-pyrrol-1-yl)-2H-chromen-2-one, and (C) 3-(1H-imidazol-1-yl)-6,7-dimethoxy-2H-chromen-2-one. In silico studies suggest that compounds B and C may exhibit antagonistic interactions at the α₂-adrenergic, GPVI collagen, and P₂Y₁₂ ADP receptors. Additionally, molecular docking indicates essential interactions between the compounds and the GPIIb/IIIa fibrinogen receptor.