Photodynamic Therapy (PDT) is recognized for its exceptional effectiveness as a promising cancer treatment method. However, it is noted that overexposure to the dosage and sunlight in traditional PDT ...can result in damage to healthy tissues, due to the low tumor selectivity of currently available photosensitizers (PSs). To address this challenge, we introduce herein a new strategy where the small molecule-targeted agent, erlotinib, is integrated into a boron dipyrromethene (BODIPY)-based PS to form conjugate 6 to enhance the precision of PDT. This conjugate demonstrates optical absorption, fluorescence emission, and singlet oxygen generation efficiency comparable to the reference compound 7, which lacks erlotinib. In vitro studies reveal that, after internalization, conjugate 6 predominantly accumulates in the lysosomes of HepG2 cells, exhibiting significant photocytotoxicity with an IC50 value of 3.01 µM. A distinct preference for HepG2 cells over HELF cells is observed with conjugate 6 but not with compound 7. In vivo experiments further confirm that conjugate 6 has a specific affinity for tumor tissues, and the combination treatment of conjugate 6 with laser illumination can effectively eradicate H22 tumors in mice with outstanding biosafety. This study presents a novel and potential PS for achieving precise PDT against cancer.
A facile and versatile amination of fluorobenzenes has been developed in good to excellent yields under microwave irradiation in NMP without strong base and catalyst. It is remarkable that ...multi-fluorine substituted benzenes can produce the regioselective mono-substituted products. Display omitted
► The amination of fluorobenzenes has been developed under microwave irradiation. ► A facile method was established for preparing fluorine substituted anilines. ► No strong base and catalyst were used in this method. ► The presence of various position of halogen enhanced the leaving ability of fluorine. ► All the reactions produced mono-substituted aniline derivatives as the only product.
A facile and versatile amination of fluorobenzenes has been developed in good to excellent yields under microwave irradiation in N-methylpyrrolidinone (NMP) without strong base and catalyst. The presence of additional halogen atom(s) enhanced the leaving ability of fluorine and meta fluorine gave higher activation than the ortho. It is remarkable that 1,2,3-trifluorobenzene, 1,2,4-trifluorobenzene and 1,2,4,5-tetrafluorobenzene can produce the regioselective mono-substituted products.
Novel 4-thiophenyl quinoline-based HMG CoA reductase inhibitors were synthesized. Some compounds showed great potency in vitro.
A series of novel 4-thiophenyl quinoline-based mevalonolactone ...derivatives were synthesized from ethyl 6,7,8-trisubstituted-4-chloro-quinoline-3-carboxylates by several reactions and evaluated for their ability to inhibit the rat HMG CoA reductase in vitro. It was found that substitution with a variety of thiophenyl groups at position 4 in quinoline resulted in retention or enhancement of the inhibition and the preferable groups were 4-isopropyl-thiophenyl and 3-methoxy-thiophenyl. (4
R,6
S)-6-(
E)-2-(6,7,8-trifluoro-4-isopropylthiophenyl-quinoline-3-yl)-ethenyl-3,4,5,6-tetrahydro-4-hydroxy-2
H-pyran-2-one (
A16) and (4
R, 6
S)-6-(
E)-2-(6-fluoro-4,7-di-(3-methoxy-thiophenyl)-quinoline-3-yl)-ethenyl-3,4,5,6-tetrahydro-4-hydroxy-2
H-pyran-2-one (
A23) were approximately three times more potent than rosuvastatin or pitavastatin in inhibiting HMG CoA reductase and selected as the hypocholesterolemic candidates for further evaluation.
A series of xanthine derivatives in which a methylene was inserted at position 8 of xanthine scaffold was synthesized and evaluated as inhibitors of dipeptidyl peptidase 4 (DPP-4) for the treatment ...of type 2 diabetes. As the results of structure–activity relationship (SAR) study of the series, the compounds with 4-methyl-quinazoline-2-yl-methyl group at N-1 position and 2-aminoethylaminomethyl group gave better activities. Compounds H4 and H9 showed good DPP-4 inhibition and more than 100-fold selectivity over DPP-7 and DPP-8.
Large-scale implementation of electrochemical water splitting for hydrogen evolution requires cheap and efficient catalysts to replace expensive platinum. However, catalysts that work well at high ...current densities with ultrafast intrinsic activities is still the central challenge for hydrogen evolution. An ideal case is to use single atoms on monolayer two-dimensional (2D) materials, which simplifies the system and in turn benefits the mechanism study, but is a grand challenge to synthesize. Here, we report a universal cold hydrogen plasma reduction method for synthesizing different single atoms sitting on 2D monolayers. In the case of molybdenum disulfide, we design and identify a type of active site, i.e., unsaturated Mo single atoms on cogenetic monolayer molybdenum disulfide. The catalyst shows exceptional intrinsic activity with a Tafel slope of 36.4 mV dec–1 in 0.5 M H2SO4 and superior performance at a high current density of 400 mA cm–2 with an overpotential of ∼260 mV, based on single flake microcell measurements. Theoretical studies indicate that coordinately unsaturated Mo single atoms sitting on molybdenum disulfide increase the bond strength between adsorbed hydrogen atoms and the substrates through hybridization, leading to fast hydrogen adsorption/desorption kinetics and superior hydrogen evolution activity. This work shines fresh light on preparing highly efficient electrocatalysts for water splitting and other electrochemical processes, as well as provides a general method to synthesize single atoms on two-dimensional monolayers.
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Tirzepatide, the first approved dual GLP-1/GIP receptor agonist (RA), has achieved better clinical outcomes than other GLP-1RAs. However, it is an imbalanced dual GIP/GLP-1 RA, and it ...remains unclear whether the degree of imbalance is optimal. Here, we present a novel long-acting dual GLP-1/GIP RA that exhibits better activity than tirzepatide toward GLP-1R. A candidate conjugate, D314, identified via peptide design, synthesis, conjugation, and experimentation, was evaluated using chronic studies in db/db and diet induced obese (DIO) mice. D314 achieved favorable blood glucose and body weight-lowering effects, equal to those of tirzepatide. Its half-life in dogs (T1/2: 78.3 ± 14.01 h) reveals its suitability for once-weekly administration in humans. This preclinical study suggests the potential role of D314 as an effective agent for treating T2DM and obesity.
A method for separation and determination of 32 fentanyl‐related substances, including seven sets of isomeric fentanyl analogues, was developed using ultra‐high‐performance liquid chromatography ...coupled with quadrupole‐orbitrap high‐resolution mass spectrometry. The collision energy, chromatographic column, and mobile phase were optimized. All compounds were efficiently flushed out of a universal C18 column with a soft gradient consisting of solvent A (2 mM ammonium formate and 0.1% formic acid in water) and solvent B (2 mM ammonium formate and 0.1% formic acid in methanol) in only 20 min, achieving excellent resolution. Detection and analysis were carried out simultaneously in the positive ion mode using the full scan and data‐dependent tandem mass spectrometry modes with a normalized collision energy of 40. The method was validated in terms of limit of detection, limit of quantification, linearity, accuracy, and precision. For all fentanyl‐related substances, the limit of detection (0.5 ng/mL) and limit of quantification (1 ng/mL) were adequate for screening and quantification in daily drug control. Calibration curves for all compounds were established in the range of 1–500 ng/mL. The intra‐ and interday precision (RSD%) were within 0.4–2.3 and 0.7‐2.7%, respectively. The accuracy ranged from 99 to 106%. The method was applied to analyze seized drug samples.
This research examined the ways that ethnic minorities are depicted in mainstream media representations in China and how the public accepts and consumes such depictions. It provides a case study of ...the Inner Mongolian singer Ayanga, who made his debut in the media in 2012 and gained great popularity in a musical talent show in 2018. The thesis put various media texts produced by related fans communities into a database for analysis. By looking into the media strategies used by the state power structure and the majority ethnic group of China, a country where the dominant mainstream Han group makes up over 90% of the national population, the study discovers how representations of ethnic minorities help to construct the Han's subjectivity in China's nationality.
Economic syntheses of sitagliptin phosphate monohydrate, acknowledged as the first dipeptidyl peptidase 4 (DPP-4) inhibitor, have been achieved in an overall yield of 42.4% in four steps from ...1-{3-(trifluoromethyl)-5,6-dihydro-1,2,4triazolo4,3-apyrazin-7(8H)-yl}-4-(2,4,5-trifluorophenyl)butane-1,3-dione. The key stereoselective reduction of this process was carried out by NaBH
4
/HCOOH instead of expensive and toxic catalysts or ligands.
Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.
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