The annulation reactions of enaminones with quinonediimides/quinoneimides for the selective synthesis of indoles and 2-aminobenzofurans have been realized. With Zn(
ii
) catalysis, quinonediimides ...reacted with enaminones to give indoles
via
HNMe
2
-elimination-based aromatization. With Fe(
iii
) catalysis, the reactions of quinoneimides with enaminones provided 2-aminobenzofurans
via
a key dehydrogenative aromatization.
The selectivity tunable synthesis of functionalized indoles and benzofurans has been achieved via the reactions of enaminones with quinonediimides and quinoneimides under modified conditions, respectively.
With 2‐hydroxyphenyl‐functionalized enaminones and thiophenols as the starting materials, the facile synthesis of 3‐sulfenylated chromones has been realized through a KIO3‐catalyzed domino reaction ...of C−H sulfenylation and subsequent C−N‐cleavage‐based C−O bond formation. The reaction was performed under transition‐metal‐free conditions in ethyl lactate, a bioavailable ecofriendly medium.
Green synthesis: A domino reaction of C−H sulfenylation and C−N‐cleavage‐based annulation of enaminones allows the concise construction of 3‐sulfenylated chromones under transition‐metal‐free conditions (EL: ethyl lactate).
The CC double bond cleavage of enaminones has been realized under ambient conditions through visible‐light catalysis in the presence of Rose Bengal, which leads to the synthesis of a class of ...1,2‐diketones without using any metal catalyst. In addition, the one‐pot synthesis of quinoxalines has also been achieved under identical photocatalytic conditions by making use of the in situ generated 1,2‐diketones as intermediates.
White LED power to diketones: A sustainable synthetic protocol towards the synthesis of 1,2‐diketones is achieved by visible‐light‐induced cleavage of the CC double bond in enaminones.
The reactions between o-hydroxylphenyl-functionalized enaminones and sulfonyl hydrazines providing 3-sulfenylated chromones via domino chromone ring construction and C(sp2)–H bond sulfenylation have ...been achieved under transition-metal-free conditions by using KIO3 as the only catalyst.
C50 carotenoids are promising bioactive compounds produced by halophilic archaea. Relevant studies have focused on their outstanding antioxidant activity, whereas the extraction process has received ...less attention. In this study, the effect of factors on carotenoid extraction efficiency was explored through single-factor and orthogonal experiments. The results showed that the C50 carotenoids were effectively extracted by suspending and homogenizing cell pellets in methanol (1:30, w-v) for 10 min, subsequently incubating at 30 °C for 30 min in the dark, finally centrifuging and drying over vacuum rotary evaporation at 30 °C in the dark. The carotenoid content increased 1.84 times by the above procedure than that before optimization. Moreover, the UVVis spectra, TLC and HPLCMS analysis revealed that the main component of carotenoids extracted from Halorubrum sp. HRM-150 was bacterioruberin (84.12 %), followed by monoanhydrobacterioruberin (15.13 %). Both carotenoid extract and bacterioruberin exhibited antioxidant capacity, which were significantly higher than that of astaxanthin (p < 0.05) by scavenging assays of 2,2-azinobis-3-ethyl-benzothiazole-6-sulfonic acid, 2,2-diphenyl-1-picrylhydrazyl and hydroxyl radicals. In addition, the hydroxyl radical scavenging rate of bacterioruberin was significantly higher than that of carotenoid extract (p < 0.01), indicating its potential activity against or delaying diseases caused by reactive oxygen species. C50 carotenoids (especially BR) have great application prospects in human health due to their excellent antioxidant capacity.
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•Bacterioruberin (BR) was the predominant carotenoid in Halorubrum, accounting for 84.12 %.•The carotenoid content was enhanced 1.84 times after extraction optimization.•C50 carotenoid extract displayed higher antioxidant activity than astaxanthin.•BR exhibited higher scavenging rates of·OH radicals than carotenoid extract and astaxanthin.
The A-type Aurora kinase is upregulated in many human cancers, and it stabilizes MYC-family oncoproteins, which have long been considered an undruggable target. Here, we describe the design and ...synthesis of a series of pyrimidine-based derivatives able to inhibit Aurora A kinase activity and reduce levels of cMYC and MYCN. Through structure-based drug design of a small molecule that induces the DFG-out conformation of Aurora A kinase, lead compound 13 was identified, which potently (IC50 < 200 nM) inhibited the proliferation of high-MYC expressing small-cell lung cancer (SCLC) cell lines. Pharmacokinetic optimization of 13 by prodrug strategies resulted in orally bioavailable 25, which demonstrated an 8-fold higher oral AUC (F = 62.3%). Pharmacodynamic studies of 25 showed it to effectively reduce cMYC protein levels, leading to >80% tumor regression of NCI-H446 SCLC xenograft tumors in mice. These results support the potential of 25 for the treatment of MYC-amplified cancers including SCLC.
The synthesis of polyfunctionalized aminothioalkenes has been realized via the direct C–H sulfenylation of enaminones and analogous enamines. These cross-coupling reactions have been achieved by ...simple KIO3 catalysis under aerobic conditions without employing any transition metal catalyst or additional oxidant. The employment of bio-based green solvent ethyl lactate as the reaction medium constitutes another sustainable feature of the present work.
Both bacteria and autophagy are implicated in inflammatory bowel disease (IBD) pathogenesis. However, how bacteria crosstalk with autophagy signaling remains largely known, especially in intestinal ...mucosa. This study aimed to profile the internal complex autophagy signaling cascade and their external correlation with these bacteria, and consequently provide a systematic and precise target for future IBD diagnosis and therapy. We found the Ulcerative colitis (UC) patients exhibited more severe dysbiosis than the Crohn's disease (CD) patients, as represented by alpha diversity, community phenotypes, and functional annotation compared with the control population. Meanwhile, CD patients showed greater transcriptional signaling activities of autophagy, endoplasmic reticulum (ER) stress, and bile acid production. Dominant bacteria (e.g.,
,
,
, and
) were positively correlated and low-abundance bacteria (e.g.,
,
,
, and
) were negatively correlated with the autophagy signaling cascade (184 autophagy genes, 52 ER stress genes, and 22 bile acid production genes). Our observations suggested UC patients showed temporary and widespread microbiota turbulence and CD patients showed processive and local autophagy activity during IBD progression. Intestinal mucosa-colonizing bacteria were correlated with the bile/ER stress/autophagy signaling axis in IBD pathogenesis.
Acute myeloid leukemia (AML) is a prevalent hematological malignancy among adults. Recent studies suggest that the length of telomeres could significantly affect both the risk of developing AML and ...the overall survival (OS). Despite the limited focus on the prognostic value of telomere-related genes (TRGs) in AML, our study aims at addressing this gap by compiling a list of TRGs from TelNet, as well as collecting clinical information and TRGs expression data through the Gene Expression Omnibus (GEO) database. The GSE37642 dataset, sourced from GEO and based on the GPL96 platform, was divided into training and validation sets at a 6:4 ratio. Additionally, the GSE71014 dataset (based on the GPL10558 platform), GSE12417 dataset (based on the GPL96 and GPL570 platforms), and another portion of the GSE37642 dataset (based on the GPL570 platform) were designated as external testing sets. Univariate Cox regression analysis identified 96 TRGs significantly associated with OS. Subsequent Lasso-Cox stepwise regression analysis pinpointed eight TRGs (MCPH1, SLC25A6, STK19, PSAT1, KCTD15, DNMT3B, PSMD5, and TAF2) exhibiting robust predictive potential for patient survival. Both univariate and multivariate survival analyses unveiled TRG risk scores and age as independent prognostic variables. To refine the accuracy of survival prognosis, we developed both a nomogram integrating clinical parameters and a predictive risk score model based on TRGs. In subsequent investigations, associations were emphasized not solely regarding the TRG risk score and immune infiltration patterns but also concerning the response to immune-checkpoint inhibitor (ICI) therapy. In summary, the establishment of a telomere-associated genetic risk model offers a valuable tool for prognosticating AML outcomes, thereby facilitating informed treatment decisions.
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