Direct binding and characterization of laccase onto iron oxide nanoparticles.

Iron oxide nanoparticles (IONPs) exhibit unique magnetic properties and possess a high surface-to-volume ratio, making them ideal candidates for the conjugation of substances, including enzymes. Laccase (EC 1.10.3.2), an oxidative enzyme with diverse applications, presents an opportunity for enhancing stability and reusability through innovative immobilization techniques, thus reducing overall process costs. In this study, we employed a direct binding procedure via carbodiimide activation to conjugate laccase onto IONPs synthesized using thermal chemical coprecipitation. Stabilization of the nanoparticles was achieved using thioglycerol and polyvinyl alcohol (PVA) as capping agents. Characterization of the synthesized nanoparticles was conducted using UV-spectroscopy, Fourier transform infrared spectroscopy (FTIR), x-ray diffraction, scanning electron microscopy, and energy dispersive x-ray spectroscopy. FTIR spectroscopy analysis confirmed successful laccase binding to magnetic nanoparticles, with binding efficiencies of 90.65% and 73.02% observed for thioglycerol and PVA capped IONPs, respectively. Furthermore, the conjugated enzyme exhibited remarkable stability, retaining nearly 50% of its initial activity after 20 reuse cycles. This research demonstrates that immobilizing laccase onto IONPs enhances its activity, stability, and reusability, with the potential for significant cost savings and expanded applications in various fields.

Hit discovery of novel 2-phenyl-substituted 4-amino-6,7-dihydro-5H-cyclopenta[d]pyrimidines as potential anti-glioblastoma therapeutics: Design, synthesis, biological evaluation, and computational screening.

Glioblastoma multiforme (GBM) is a highly-aggressive, dreadful disease with poor prognosis and disappointing clinical success. There is an unmet medical need of molecularly-targeted therapeutics for GBM treatment. In the present work, a series of novel 2-phenyl-substituted 4-amino-6,7-dihydro-5H-cyclopenta[d]pyrimidines was designed, synthesized, purified, characterized, and evaluated for cytotoxicity against glioblastoma cell line U87-MG. The design process (virtual library enumeration around the core, physicochemical and molecular property prediction/calculation of the designs, filtering the undesirable ones, and the diversity analyses of the lead-like designs), was carefully curated so as to obtain a set of structurally-diverse, novel molecules (total 20), with a particular focus on the relatively unexplored core structure, 6,7-dihydro-5H-cyclopenta[d]pyrimidine. The preliminary screening was done using MTT assay at 10 and 100 µM concentrations of the title compounds F1 -F20 and positive control cisplatin, which yielded six hits (% inhibition at 10 µM: ~50%)-F2 , F3 , F5 , F7 , F15 , and F20 , which were taken up for IC50 determination. The top hits F2 and F7 (IC50 < 10 µM) were further used for computational studies such as target prediction, followed by their molecular docking in the binding sites of the top-3 predicted targets (epidermal growth factor receptor kinase domain, cyclin-dependent kinase 2 [CDK2]) /cyclin E, and anaplastic lymphoma kinase [ALK]). The docking pose analyses revealed interesting trends. The relatively planar core structure, presence of favorable hinge-binding substructures, basic groups, all added up, and culminated in appreciable cytotoxicity against GBM cell line.

Synthesis and Functionalization of Coumarin-Pyrazole Scaffold: Recent Development, Challenges, and Opportunities.

Heterocycles are the main structural motif of DNA and RNA and play a crucial role in various chemical reactions of metabolisms. Therefore, heterocyclic compounds show good physiological and pharmacological properties. Coumarin and pyrazole scaffolds are present in many commercial drug molecules and natural products. This review overviews the progress made in the synthesis and functionalization of the coumarin- pyrazole hybrid heterocycle. It also includes discussion on the possible reactive sites of heterocycles, functionalization, and mechanistic pathways to incorporate pyrazole pharmacophore unit in synthesis. Several synthesis and biological studies reveal that the combination of the coumarin-pyrazole moiety is a prominent structural motif to find lead compounds in drug discovery.