Benzimidazoles Containing Piperazine Skeleton at C-2 Position as Promising Tubulin Modulators with Anthelmintic and Antineoplastic Activity.

Benzimidazole anthelmintic drugs hold promise for repurposing as cancer treatments due to their interference with tubulin polymerization and depolymerization, manifesting anticancer properties. We explored the potential of benzimidazole compounds with a piperazine fragment at C-2 as tubulin-targeting agents. In particular, we assessed their anthelmintic activity against isolated muscle larvae and their effects on glioblastoma (U-87 MG) and breast cancer (MDA-MB-231) cell lines.

R346K Mutation in the Variant of SARS-CoV-2 Alters the Interactions with Monoclonal Antibodies from Class 2: A Free Energy Perturbation Study.

The variant of SARS-CoV-2 has been recently classified as a variant of interest (VOI) by the World Health Organization (WHO) but limited data are available at the moment. In particular, special attention was given to the R346K mutation located in the receptor binding domain (RBD). In the current study, we performed free energy perturbation (FEP) calculations to elucidate its possible impact on a set of neutralizing monoclonal antibodies (mAbs) that have been shown to be strong inhibitors of the most other known COVID-19 variants.

N501Y and K417N Mutations in the Spike Protein of SARS-CoV-2 Alter the Interactions with Both hACE2 and Human-Derived Antibody: A Free Energy of Perturbation Retrospective Study.

The N501Y and K417N mutations in the spike protein of SARS-CoV-2 and their combination gave rise to questions, but the data on their mechanism of action at the molecular level were limited. In this study, we present free energy perturbation (FEP) calculations, performed at the end of December 2020, for the interactions of the spike S1 receptor-binding domain (RBD) with both the ACE2 receptor and an antibody derived from COVID-19 patients. Our results showed that the S1 RBD-ACE2 interactions were significantly increased whereas those with the STE90-C11 antibody dramatically decreased.

1H-benzimidazole-2-yl hydrazones as tubulin-targeting agents: Synthesis, structural characterization, anthelmintic activity and antiproliferative activity against MCF-7 breast carcinoma cells and molecular docking studies.

In the present study, fifteen benzimidazolyl-2-hydrazones 7a-7o of fluoro-, hydroxy- and methoxy-substituted benzaldehydes and 1,3-benzodioxole-5-carbaldehyde were synthesized and their structure was identified by IR, NMR, and elemental analysis. The compounds 7j 2-(3-hydroxybenzylidene)-1-(5(6)-methyl-1H-benzimidazol-2-yl)hydrazone and 7i 2-(3-hydroxybenzylidene)-1-(1H-benzimidazol-2-yl)hydrazone have exerted the strongest anthelmintic activity (100% after 24 h incubation period at 37 °C) against isolated muscle larvae of Trichinella spiralis in an in vitro experiment. The in vitro cytotoxicity assay towards MCF-7 breast cancer cells and mouse embryo fibroblasts 3T3 showed that the studied benzimidazolyl-2-hydrazones exhibit low to moderate cytotoxic effects.

Discovery of new AKT1 inhibitors by combination of structure based virtual screening approaches and biological evaluations.

Communicated by Ramaswamy H. Sarma.