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In clinical diagnosis, fluorescent particles are applied to detect analytes in biofluids, such as blood and saliva. However, current fluorescence detection methods have not been optimized to account for the overlapping autofluorescence peaks of biological substances. Gold and silver nanoclusters are known to the novel fluorescent materials and their emission wavelengths depend on cluster size. In this study, we developed fluorescent silica nanoparticles using gold–silver alloy nanoclusters and chitosan (CS) (NH₂-SiO₂@Au@CS@AuAg) by the layer-by-layer method. Under UV-light irradiation at 365 nm, the emission wavelength of NH₂-SiO₂@Au@CS@AuAg reached 750 nm in the near-IR region. Scanning electron microscopy images revealed that the shape of NH₂-SiO₂@Au@CS@AuAg was uniform and spherical. The fluorescence spectrum of horse blood obtained in the presence of NH₂-SiO₂@Au@CS@AuAg contained a specific fluorescence peak attributed to NH₂-SiO₂@Au@CS@AuAg, which was distinguishable from the autofluorescence peaks. These results showed that NH₂-SiO₂@Au@CS@AuAg has advantageous fluorescence properties for clinical diagnostic applications.

Although curcumin and its analogs exhibit anticancer activity, they are still not used as anticancer drugs because of their water insolubility and extremely poor bioavailability. This study describes the development of water-soluble prodrugs of GO-Y030, a potent antitumor C5-curcuminoid, in an attempt to enhance its bioavailability. These prodrugs release the parent compound via a retro-thia-Michael reaction. To endow sufficient hydrophilicity onto GO-Y030 via a single thia-Michael reaction of an aqueous entity, we used a modified glycoconjugate with a thiol group. The water-solubilizing motif was installed on GO-Y030 by the thia-Michael reaction of propargyl-polyethylene glycol (PEG)-thiol and subsequent click chemistry (CuAAC) reaction with 1-glycosyl azide. Turbidity measurements revealed a significantly improved water solubility of the prodrugs, demonstrating that disaccharide conjugates were completely dissolved in water at 100 µM. Their cytotoxicity was comparable to that of the parent compound GO-Y030, indicating the gradual in situ release of GO-Y030. The release of GO-Y030 from GO-Y199 via the retro-thia-Michael reaction was demonstrated through a degradation study in water. Our retro-thia-Michael reaction-based prodrug system can be used for targeting cancer cells.

A series of 2-azolylmethylene-3-(2H)-benzofuranone derivatives, 2-indolylmethylene-3-(2H)-benzofuranone and 2-pyrrolylmethylene-3-(2H)-benzofuranone derivatives, were synthesized, and their monoamine oxidase (MAO) A and B inhibitory activities were evaluated. Compounds 1b, 3b, 6b, 7b, and 10b showed strong inhibitory activity against MAO-A, and compound 3b showed the highest potency and selectivity, with an IC₅₀ value of 21 nM and a MAO-A selectivity index of 48. Compounds 3c, 4c, 9a, 9c, 10c, 11a, and 11c showed strong inhibitory activity against MAO-B, and compound 4c showed the highest potency and selectivity, with an IC₅₀ value of 16 nM and a MAO-B selectivity index of >1100. Further analysis of these compounds indicated that compound 3b for MAO-A and compound 4c for MAO-B were competitive inhibitors, with K_i values of 10 and 6.1 nM, respectively. Furthermore, computational analyses, such as quantitative structure–activity relationship (QSAR) analysis of the 2-azolylmethylene-3-(2H)-benzofuranone derivatives conducting their pIC₅₀ values with the Molecular Operating Environment (MOE) and Mordred, and molecular docking analysis using MOE-Dock supported that the 2-azolylmethylene-3-(2H)-benzofuranone derivatives are a privileged scaffold for the design and development of novel MAO inhibitors.

For powder compaction, the Kawakita equation has been used to estimate the powder behavior inside the die. The compression pressure exerted on powders is not homogeneous because of the friction on the die wall. However, the yield pressure and porosity estimated using the Kawakita equation are defined based on the assumption that homogeneous voids and compression pressure are distributed throughout the powder bed. In this study, an extended Kawakita equation was derived by considering the variation in the compression pressure as it corresponds to the distance from the loading punch surface. The yield time section estimated from the extended Kawakita equation was wider than that which was estimated via the classical equation. This result is consistent with the assumptions used to derive the extended Kawakita equation. Furthermore, a comparison of the porosity changes before and after the yield pressure was applied indicate that the direct cause of the yield is the spatial constraints of the powder particles. Equivalent stresses were defined to clarify the critical factor that constitutes the extended Kawakita equation. As a result, “taking into account the die wall friction” was considered to be the critical factor in the extended Kawakita equation. As these findings were theoretically determined by the extended Kawakita equation, a useful model was derived for a better understanding of powder compaction in die.

A novel tricyclic polyketide, curvulanone (1), was isolated from the marine-derived fungus Curvularia aeria. The structure of 1 was determined by NMR and single-crystal X-ray crystallography. 1 had a cyclopentabenzopyranone with 3-acetic acid structure that is rarely found in natural compounds. Monoamine oxidase and sirtuin 1 inhibitory test was exhibited and 1 showed their inhibitory activity.

The oxidative cleavage reaction of pyrrolidine-2-methanols to γ-lactams has been described. In this reaction, [4-iodo-3-(isopropylcarbamoyl)phenoxy]acetic acid and powdered Oxone (2KHSO₅·KHSO₄·K₂SO₄) were employed as the catalyst and co-oxidant, respectively. The reaction is efficient and environmentally benign because it produces various lactams from readily available substrates in moderate to excellent yields using organocatalyst and inorganic non-toxic co-oxidant.

Two novel series of quinazolinone-based hybrids, including quinazolinone-1,3,4-oxadiazoles (10a–l) and quinazolinone-1,3,4-oxadiazole-benzimidazoles (8a–e), were designed and synthesized and their cytotoxic activities against three human cancer cell lines, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MCF-7), were evaluated. The cytotoxic assays revealed that 10i with a lipophilic 4-fluoro-phenyl moiety at the C-2 position of the quinazolinone ring displayed good cytotoxicities against the A549 and MCF-7 cell lines, while 8b–d with the thioether-linked benzimidazole moiety incorporated on the right side of the oxadiazole ring induced comparable stronger activities toward the MCF-7 cell line, relative to the simple two-heterocycle-containing hybrid 10i. These novel quinazolinone-based hybrids could be considered as lead compounds that merit further optimization and development as anti-cancer agents.

This study investigates the stability of nitrazepam (NZP), a benzodiazepine drug, under basic conditions, since alkaline putrefactive amines and ammonia are produced once bodies are left to decompose for a long period postmortem after a murder involving NZP or an accidental overdose of NZP. The degradation of NZP in an aqueous alkaline solution was investigated by LC/photodiode array detector (PDA) where the NZP degradation product was isolated and purified by solid-phase extraction using Oasis^® MCX, and its chemical structure was determined by LC/time-of-flight (TOF)-MS, NMR spectroscopy, and single-crystal X-ray crystallography. The results revealed that NZP was immediately degraded under basic conditions with 2-amino-5-nitrobenzophenone being an intermediate which further degraded to provide 2-hydroxy-5-nitrobenzophenone as the final degradation product. These results are expected to be useful in clinical chemistry and forensic science, such as the detection of drugs during postmortem examination and suspected addiction.

Twenty natural-product-like 2,8-dioxabicyclo[3.3.1]nonane derivatives were synthesized and their neuroprotective activities were tested using human monoamine oxidases (MAO) A and B and acetyl and butyryl cholinesterases (ChE). Compound 1s showed inhibitory activity for MAO-A, MAO-B and acetylcholinesterase (AChE) (IC₅₀ values 34.0, 2.3 and 11.0 µM, respectively). The inhibition mode of (−)-1s for MAO-B was investigated. Chiral HPLC of (±)-1s separated the enantiomers and (−)-1s showed MAO-B inhibitory activity. Molecular docking simulation of (−)-1s and MAO-B revealed the binding mode.

Triplex DNA formation has generated much interest as a genomic targeting tool that directly targets duplex DNA. However, fundamental limitations in the base pairs of target duplex DNA sequences that can form stable triplex DNA have limited the application. Recently, we have reported on the recognition of CG and ^5mCG base pairs by artificial nucleic acid derivatives with a 2′-deoxynebularine skeleton. Therefore, we attempted to explore the basic skeleton that is important for the development of new artificial nucleic acids allowing for the recognition of TA base pairs. In this study, we focused on a benzimidazole skeleton and introduced a hydroxyl group to enable one-point hydrogen bonding. We have synthesized artificial nucleoside analogues with hydroxyl group on the benzimidazole and incorporated their amidite derivatives into triplex forming oligonucleotides (TFOs). The gel shift assay was performed to evaluate the triplex DNA formation ability of synthesized TFOs, and TFOs containing hydroxybenzimidazole were successfully recognized TA base pairs for all four different sequences. Moreover, compared to the results for the TFOs containing benzimidazole, which suggested hydrogen bonding formation at the hydroxyl group. Therefore, hydroxybenzimidazole would be an important artificial nucleic acid skeleton for TA base pair recognition.