In this work we aimed to perform an in silico predictive screening, docking and molecular dynamic study to identify 1,2,3-triazole-phthalimide derivatives as drug candidates against SARS-CoV-2. The in silico prediction of pharmacokinetic and toxicological properties of hundred one 1,2,3-triazole-phtalimide derivatives, obtained from SciFinder® library, were investigated. Compounds that did not show good gastrointestinal absorption, violated the Lipinski's rules, proved to be positive for the AMES test, and showed to be hepatotoxic or immunotoxic in our ADMET analysis, were filtered out of our study. The hit compounds were further subjected to molecular docking on SARS-CoV-2 target proteins. The ADMET analysis revealed that 43 derivatives violated the Lipinski’s rules and 51 other compounds showed to be positive for the toxicity test. Seven 1,2,3-triazole-phthalimide derivatives (A7, A8, B05, E35, E38, E39, and E40) were selected for molecular docking and MFCC—ab initio analysis. The results of molecular docking pointed the derivative E40 as a promising compound interacting with multiple target proteins of SARS-CoV-2. The complex E40-M^pro was found to have minimum binding energy of −10.26 kcal/mol and a general energy balance, calculated by the quantum mechanical analysis, of −8.63 eV. MD simulation and MMGBSA calculations confirmed that the derivatives E38 and E40 have high binding energies of −63.47 ± 3 and −63.31 ± 7 kcal/mol against SARS-CoV-2 main protease. In addition, the derivative E40 exhibited excellent interaction values and inhibitory potential against SAR-Cov-2 main protease and viral nucleocapsid proteins, suggesting this derivative as a potent antiviral for the treatment and/or prophylaxis of COVID-19. Communicated by Ramaswamy H. Sarma

Visceral leishmaniasis (VL), caused by protozoa of the genus Leishmania, remains a significant public health concern due to its potentially lethal nature if untreated. Current chemotherapy options are limited by severe toxicity and drug resistance. Derivatives of 1,2,4-oxadiazole have emerged as promising drug candidates due to their broad biological activity. This study investigated the effects of novel 1,2,4-oxadiazole derivatives (Ox1–Ox7) on Leishmania infantum, the etiological agent of VL. In silico predictions using SwissADME suggest that these compounds have high oral absorption and good bioavailability. Among them, Ox1 showed the most promise, with higher selectivity against promastigotes and lower cytotoxicity towards L929 fibroblasts and J774.G8 macrophages. Ox1 exhibited selectivity indices of 18.7 and 61.7 against L. infantum promastigotes and amastigotes, respectively, compared to peritoneal macrophages. Ultrastructural analyses revealed severe morphological damage in both parasite forms, leading to cell death. Additionally, Ox1 decreased the mitochondrial membrane potential in promastigotes, as shown by flow cytometry. Molecular docking and dynamic simulations indicated a strong affinity of Ox1 for the L. infantum CYP51 enzyme. Overall, Ox1 is a promising and effective compound against L. infantum.

Nanocomposites combining the coordination polymer [Zn ₂ (1,3‐bdc)(Bzim) ₂ ] as support with metallic nanoparticles—Cu (0.13 wt %), Ag (0.028 wt %), or Au (0.092 wt %)—were successfully synthesized using the “ship‐in‐bottle” method, and characterized by XRD, SEM, TEM, FTIR, ICP‐OES, and BET. The incorporation of MNPs did not alter the stability and structure of the support. In the evaluation of biocidal agents, nanocomposites showed enhanced bactericidal activity by up to thirteen times compared to MNPs without support and up to sixteen times regarding the antibiotic amoxicillin. Furthermore, the cytotoxicity of the materials was evaluated in fibroblasts and macrophages using the MTT assay. Our findings indicate that the cytotoxicity of MNPs/[Zn ₂ (1,3‐bdc)(Bzim) ₂ ] materials is dose‐dependent. At concentrations ≤ CC50, these nanomaterials exhibited excellent cytocompatibility. Notably, the Ag‐based nanocomposite demonstrated significant antibacterial activity without substantial cytotoxicity, even at higher doses.