A new series of pyrazoline derivatives 1b–12b was designed, synthesized and evaluated for antiproliferative activity against three cancer cell lines (HepG-2, Hela and A549). Additionally, NIH/3T3 cell cytotoxicity were tested and the structure activity relationships (SARs) were also determined. Among these new derivatives, the compounds 3-(4-fluorophenyl)-5-(3,4,5-trimethoxythiophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (1b) and 3-(4-chlorophenyl)-5-(3,4,5-trimethoxythiphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (2b) showed the best activity against HepG-2 cells, with IC50 values of 6.78 μM and 16.02 μM, respectively. They also displayed potent activity against Hela cells; meanwhile, 3-(4-chlorophenyl)-5-(3-bromo-4-hydroxy-5-methoxythiophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (5b) and 3-(4-bromo-phenyl)-5-(3-bromo-4-hydroxy-5-methoxythiophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (6b) were also identified as promising anticancer agents against A549 cells owing to their notable inhibitory effect, compared with cisplatin (IC50 = 29.48 μM). Furthermore, it was also found that compounds 1b and 2b had low cytotoxicity against NIH/3T3 cells and further mechanistic studies revealed that 1b arrested HepG-2 cells cycle at the G2/M phase at high concentrations and induced apoptosis in HepG-2 cells. Moreover, 1b upregulated protein expression level of cleaved caspase-3, cleaved PARP, Bax and p53 and downregulated protein expression level of Bcl-2 in dose-dependent way in HepG-2 cells. Thus, this study indicates that compound 1b might be a promising antitumor drug candidate.
30 December 2022 in Journal of Agricultural and Food Chemistry
The strategy of aggregation-induced emission enhancement (AIEE) has been proven to be efficient in wide areas and has recently been adopted in the field of metal nanoclusters. However, the relationship between atomically precise clusters and AIEE is still unclear. Herein, we have successfully obtained two few-atom heterometallic gold–silver hepta-/decanuclear clusters, denoted Au6Ag and Au9Ag, and determined their structures by X-ray diffraction and mass spectrometry. The nature of the AuI⋯AgI interactions thereof is demonstrated through energy decomposition analysis to be far-beyond typical closed-shell metal–metal interaction dominated by dispersion interaction. Furthermore, a positive correlation has been established between the particle size of the nanoaggregates and the photoluminescence quantum yield for Au6Ag, manifesting AIEE control upon varying the stoichiometric ratio of Au : Ag in atomically-precise clusters.
To accelerate the pace in the field of photothermal therapy (PTT), it is urged to develop easily accessible photothermal agents (PTAs) showing high photothermal conversion efficiency (PCE). As a proof‐of‐concept, hereby a conventional strategy is presented to prepare donor–acceptor (D–A) structured PTAs through cycloaddition‐retroelectrocyclization (CA–RE) reaction, and the resultant PTAs give high PCE upon near‐infrared (NIR) irradiation. By joint experimental‐theoretical study, these PTAs exhibit prominent D–A structure with strong intramolecular charge transfer (ICT) characteristics and significantly twisting between D and A units which account for the high PCEs. Among them, the DMA‐TCNQ exhibits the strongest absorption in NIR range as well as the highest PCE of 91.3% upon irradiation by 760‐nm LED lamp (1.2 W cm−2). In vitro and in vivo experimental results revealed that DMA‐TCNQ exhibits low dark toxicity and high phototoxicity after IR irradiation along with nude mice tumor inhibition up to 81.0% through intravenous therapy. The findings demonstrate CA–RE reaction as a convenient approach to obtain twisted D–A structured PTAs for effective PTT and probably promote the progress of cancer therapies.
A full understanding of the excimer formation and structure–property relationship is essential to their development in organic electronics. Herein, we propose a template strategy for finely modulating the stacking configuration of 9-dimethylaminomethyl-10-chloroanthracene (DCAn) dimers in two-dimensional (2D) (DCAn)4Pb3Br10·2CH3(CH2)X−1OH (1-CX, 1 ≤ X ≤ 8). By introducing alcohol guests with varied carbon lengths from methanol to octanol, 1-CX with different stacking motifs of (anthracene) An dimers are obtained. The fine control on stacking parameters, including interplanar distance, overlap ratio, offset along long (dx) and short (dy) axis and intersection angle of An allows a deep insight into the key factors of excimer formation. The experimental and computational results confirm that the excimer interaction is strongly determined by the excimer types (anthracene or naphthalene) and interplanar overlap. An anthracene-type excimer is formed for 1-CX (6 ≤ X ≤ 8) once dx locates in the range of 1.08–1.23 Å, while 1-CX (1 ≤ X ≤ 5) adopts the naphthalene-type excimer for 1.55 ≤ dx ≤ 1.75 Å. Due to the stronger anthracene-type excimer interaction, a great bathochromic shift of photoluminescence is observed for 1-CX (6 ≤ X ≤ 8). Additionally, rod-like 1-CX exhibits a high aspect ratio of ∼72, thereby generating an excellent performance on optical waveguide with an optical loss coefficient of ∼3 dB mm−1. This work not only reveals the key factors on An excimer formation, but also provides an effective strategy for better understanding the structure–property of molecular excimers.