A detailed molecular-level rationale for the enantioseparation of the β-blocker levobunolol (BUN) by substituted β-cyclodextrins (β-CDs) is presented through high-level computational modeling. The calculations consistently reveal that the therapeutically active (+)-[S]-BUN enantiomer forms more stable inclusion complexes than the (-)-[R]-enantiomer with both carboxymethyl-β-CD (CM-β-CD) and sulfated-β-CD (SF-β-CD) selectors. Non-covalent interaction (NCI) reveals that the superior stability of the S-enantiomer arises from a more continuous dispersive interaction envelope and a more compact network of electrostatic and hydrogen bonds. For the most effective selector, SF-β-CD, the complexation Gibbs free energy (ΔG) in an aqueous medium is -29.5 kcal/mol for (+)-[S]-BUN versus -17.1 kcal/mol for (-)-[R]-BUN. This results in a large free energy difference (ΔΔG) of 12.4 kcal/mol, indicating exceptional enantioselectivity. The NCI isosurfaces also confirm that the S-isomer achieves optimal stereoelectronic complementarity with the host's sulfate and hydroxyl groups, showing lower steric penalties than the R-isomer. These findings provide a robust prediction of a longer electrophoretic migration time for the (+)-[S]-enantiomer and validate SF-β-CD as a highly efficient chiral selector for BUN, underscoring the power of in silico methods to elucidate complex chiral recognition mechanisms.

There is increasing evidence, from cellular, animal and human epidemiological studies, linking β-blockers with reductions in cancer growth and metastasis. Propranolol is the most investigated β-blocker for cancer; although as many different off-patent β-blockers exist, there is little commercial incentive to drive comparative clinical trials. To minimize any chance of endogenous β-agonist driven cancer growth or metastasis, theoretically, the "ideal" anti-cancer β-blocker would have high affinity, no partial agonism, and long duration of action at β2-adrenoceptors (and for some cancers, additionally at β1 or β3-AR). Using CHO cells stably expressing the wildtype and polymorphic variants of the human β1 and β1-adrenoceptors, this study assessed 35 β-blockers for the affinity and duration of binding (using 3H-CGP12177 whole cell binding) and intrinsic efficacy (CRE-gene transcription). Despite high affinity, some β-blockers had a short binding duration (e.g., alprenolol, bupranolol, levobunolol, nadolol and oxprenolol). Other compounds had substantial partial agonism (e.g., cyanopindolol, bucindolol, pindolol, pronethalol and xamoterol) and other compounds had a biphasic washout (e.g., bucindolol, timolol, carpindolol, and CGP12177) for reasons unknown. Considering all 3 factors, carazolol and ICI118551 may be more "ideal" than propranolol; however, carvedilol, with higher affinity and substantially longer duration of β2 (and β1) receptor binding than propranolol whilst maintaining low partial agonism, may be the most theoretically optimal. Furthermore, it is already widely used in cardiovascular medicine as an off-patent tablet. Thus, carvedilol may have more optimal molecular pharmacological characteristics for an "anti-cancer" β-blocker than propranolol and could enter prospective comparative clinical trials without needing any further clinical workup.

Based on its physicochemical properties and its ophthalmic route of administration, levobunolol appears to present a moderately low risk to the breastfed infant.[1] Some guidelines state that gel formulations are preferred over solutions.[2] To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue.

The β-adrenergic receptor blocking agents are an important class of drug molecules. The present study reports a new chemo and chemo-enzymatic synthetic process for (RS)-, (R)-, and (S)-bunolol, one of the potent β-adrenergic receptor blocker. In chemo-enzymatic process, CAL L4777 lipase was employed for enantioselective kinetic resolution to synthesize the enantiopure (R)-alcohol and (S)-ester from the corresponding racemic alcohol. Thereafter, the corresponding (R)-alcohol and deacylated (S)-ester were treated with tert-butylamine to produce (S)- and (R)-bunolol, respectively. In chemical approach, epichlorohydrin (RS-, R-, and S-) was used as a starting material via respective (RS)-, (S)-, and (R)-glycidyl ether as intermediates for synthesis of enantiomeric (RS)-, (R)-, and (S)-bunolol. In comparison between two approaches, it was found that the chemo-enzymatic process was more effective and resulted in enantiomeric excess of 98% with 35% yield.

Levobunolol is a β-blocker drug prescribed for the control and prevention of cardiovascular events, such as individuals with cardiac arrhythmia or a history of myocardial infarction. Creating a levobunolol-specific molecularly imprinted polymer (MIP) allows for enhanced selectivity, efficient sample preparation, controlled drug delivery, and improved sensing and detection capabilities. In this sense, the aim of this study was to obtain through DFT calculations the synthesis protocol of a MIP for levobunolol testing different functional monomers (FMs), solvents, and cross-linker agents (CLAs). The analysis of structural and energetic data led to the identification of the optimal MIP synthesis parameters, which involves the use of (trifluoromethyl)-arylic acid (TFMAA) as the functional monomer, toluene and chloroform as the solvents, and pentaerythritol triacrylate (PETRA) as the cross-linking agent. This rational design offers valuable insights for experimentalists seeking to efficiently synthesize a MIP for this important β-blocker drug.

The present study attempts to identify the prognostic value and potential mechanism of action of colorectal adenocarcinoma hypermethylated (CAHM) in thyroid carcinoma (THCA) by using the RNA sequencing (RNA-seq) dataset from The Cancer Genome Atlas (TCGA). The functional mechanism of CAHM was explored by using RNA-seq dataset and multiple functional enrichment analysis approaches. Connectivity map (CMap) online analysis tool was also used to predict CAHM targeted drugs. Survival analysis suggests that THCA patients with high CAHM expression have lower risk of death than the low CAHM expression (log-rank P=0.022, adjusted P=0.011, HR = 0.187, 95% confidence interval (CI) = 0.051-0.685). Functional enrichment of CAHM co-expression genes suggests that CAHM may play a role in the following biological processes: DNA repair, cell adhesion, DNA replication, vascular endothelial growth factor receptor, Erb-B2 receptor tyrosine kinase 2, ErbB and thyroid hormone signaling pathways. Functional enrichment of differentially expressed genes (DEGs) between low- and high-CAHM phenotype suggests that different CAHM expression levels may have the following differences in biological processes in THCA: cell adhesion, cell proliferation, extracellular signal-regulated kinase (ERK) 1 (ERK1) and ERK2 cascade, G-protein coupled receptor, chemokine and phosphatidylinositol-3-kinase-Akt signaling pathways. Connectivity map have identified five drugs (levobunolol, NU-1025, quipazine, anisomycin and sulfathiazole) for CAHM targeted therapy in THCA. Gene set enrichment analysis (GSEA) suggest that low CAHM phenotype were notably enriched in p53, nuclear factor κB, Janus kinase-signal transducer and activators of transcription, tumor necrosis factor, epidermal growth factor receptor and other signaling pathways. In the present study, we have identified that CAHM may serve as novel prognostic biomarkers for predicting overall survival (OS) in patients with THCA.

GaN nanoparticles, 3-8 nm in diameter, are prepared by a microwave-assisted reaction of GaCl3 and KNH2 in ionic liquids. Instantaneously after the liquid-phase synthesis, the β-GaN nanoparticles are single-crystalline. The band gap is blue-shifted by 0.6 eV in comparison to bulk-GaN indicating quantum confinement effects. The GaN nanoparticles show intense green emission with a quantum yield of 55 ± 3%.