Michelia alba DC is a highly valuable ornamental plant of the Magnoliaceae family. This evergreen tropical tree commonly grows in Southeast Asia and is adored for its delightful fragrance. Our study assembled the M. alba haplotype genome MC and MM by utilizing Nanopore ultralong reads, Pacbio Hifi long reads and parental second-generation data. Moreover, the first methylation map of Magnoliaceae was constructed based on the methylation site data obtained using Nanopore data. Metabolomic datasets were generated from the flowers of three different species to assess variations in pigment and volatile compound accumulation. Finally, transcriptome data were generated to link genomic, methylation, and morphological patterns to reveal the reasons underlying the differences between M. alba and its parental lines in petal color, flower shape, and fragrance. We found that the AP1 and AP2 genes are crucial in M. alba petal formation, while the 4CL, PAL, and C4H genes control petal color. The data generated in this study serve as a foundation for future physiological and biochemical research on M. alba, facilitate the targeted improvement of M. alba varieties, and offer a theoretical basis for molecular research on Michelia L.
Herein, a general and practical temperature-controlled approach for the divergent synthesis of pyrazoles and 1-tosyl-1H-pyrazoles via electrophilic cyclization in the absence of transition-metal catalysts and oxidants was developed. The desired products were obtained in moderate to excellent yields from common starting materials in both ionic liquids and ethanol by simply tuning the reaction temperature. This strategy employs easily synthesized substrates, mild reaction conditions, and excellent functional-group tolerance.
An electrochemical phenyl-carbonyl coupling reaction of aromatic aldehydes or ketones to synthesize 4-(hydroxy(phenyl)methyl)benzaldehyde derivatives has been developed. The method shows high chemoselectivity, broad functional group compatibility, atom economy, and environmental benignity and has good potential applicability.
A route for cycloaddition reaction of alkenes and tert-butyl nitrite to synthesize Δ2-isoxazolines has been developed. The overall process involves the formation of multiple chemical bonds without the use of a catalyst. This methodology features mild reaction conditions and good functional group tolerance, providing a direct approach for the preparation of isoxazolines.
A new method has been successfully developed that offers a facile and reliable approach for synthesizing (E)-2-(1-(methoxyimino)ethyl)-2-phenylbenzofuran-3(2H)-one, providing 28 compounds. This optimized process enables efficient preparation of a wide range of compounds using readily available (E)-1-(benzofuran-2-yl)ethan-1-one O-methyl oxime and iodobenzene, and provides alternative ideas for the structural modification of benzofuran ketones.
The BET (bromo and extra-terminal) family proteins are epigenetic readers and master transcription coactivators, which have attracted great interests as cancer therapeutic targets. However, there are few developed labeling toolkits that can be applied for the dynamic studies of BET family proteins in living cells and tissue slices. In order to label and study the distribution of the BET family proteins in tumor cells and tumor tissues, a novel series of environment-sensitive fluorescent probes (6a-6c) were designed and evaluated for their labeling properties. Interestingly, 6a is capable of identifying tumor tissue slices and making a distinction between the tumor and normal tissues. Moreover, it can localize to the nuclear bodies in tumor slices just like BRD3 antibody. In addition, it also played an anti-tumor role through the induction of apoptosis. All these features render 6a may compatible for immunofluorescent studies and future cancer diagnosis, and guide for the discovery of new anticancer drugs.
Nuclear Proteins , Transcription Factors , Nuclear Proteins/metabolism , Transcription Factors/metabolism , Cell Line, Tumor , Apoptosis , Cell Cycle Proteins/metabolism
A novel bis-bidentate nitronyl nitroxide radical based on triazolopyrimidine, NIT-2-TrzPm (NIT-2-TrzPm = (2-(2'-triazolopyrimidine)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxy-3-oxide)) and six new transition metal complexes of this ligand, namely [M(hfac)2(NIT-2-TrzPm)]·CH2Cl2 (M = Mn (1Mn) and Co (2Co)), [M(hfac)2]2(NIT-2-TrzPm) (M = Mn (3Mn) and Co (4Co)), [Mn(NIT-2-TrzPm)2(MeOH)2](ClO4)2·MeOH (5Mn), and [Co(NIT-2-TrzPm)2(MeOH)2]2(ClO4)4·4MeOH (6Co) were prepared and characterized structurally and magnetically. These complexes can be selectively synthesized by controlling the reaction ratio of M(hfac)2·2H2O to the radical ligand (for 1Mn to 4Co) or using metal perchlorates as the starting materials (for 5Mn and 6Co). Single crystal X-ray crystallographic analyses confirmed that 1Mn and 2Co are isostructural 3d-2p MII-radical complexes, in which the NIT-2-TrzPm radical acts as a terminal bidentate ligand chelating to one 3d ion, while 3Mn and 4Co are isostructural 3d-2p-3d MII-radical-MII complexes with the NIT-2-TrzPm radical acting as a bridging ligand between two 3d ions. For complexes 5Mn and 6Co, two NIT-2-TrzPm ligands from the equatorial positions coordinate with the metal center to form the 2p-3d-2p structures with the axial positions occupied by two methanol molecules. Magnetic analysis on the MnII complexes revealed the existence of a strong antiferromagnetic interaction between the MnII and the NIT radical spin, while weak ferromagnetic coupling for Mnâ¯Mn and Radâ¯Rad in the Mn-NIT-Mn and Rad-Mn-Rad spins was confirmed. Interestingly, although the NIT-bridged complexes 3Mn and 4Co possess significantly different magnetic anisotropy, field-induced slow magnetic relaxation can be observed in both complexes, which was assigned to the phonon bottleneck effect for 3Mn and field-induced SMM behavior for 4Co. To the best of our knowledge, 3Mn is the first example of the NIT-bridged binuclear MnII complex undergoing slow magnetic relaxation.
Potato is one of the world's most important food crops, with a time-consuming breeding process. In this study, we performed a genome-wide association (GWAS) analysis of the two important traits of potato tuber shape and eye depth, using the tetraploid potato genome (2n=4x=48) as a reference. A total of 370 potatoes were divided into three subgroups based on the principal component analysis and evolutionary tree analysis. The genetic diversity within subgroups is low (5.18×10-5, 4.36×10-5 and 4.24×10-5). Genome-wide linkage disequilibrium (LD) analysis showed that their LD is about 60 Kb. GWAS analysis identified that 146 significant single nucleotide polymorphism (SNP) loci at Chr01A1:34.44-35.25 Mb and Chr02A1:28.35-28.54 Mb regions are significantly associated with potato tuber shape, and that three candidate genes that might be related to potato tuber traits, PLATZ transcription factor, UTP-glucose-1-phosphate uridylyltransferase and FAR1 DNA-binding domain, are in the association region of Chr02A1. GWAS analysis identified 53 significant SNP loci at Chr05A2: 49.644-50.146 Mb and Chr06A2: 25.866-26.384 Mb regions with robust associations with potato tuber eye depth. Hydrolase and methyltransferases are present in the association region of Chr05A2, and three CYPs are present in the association region of Chr06A2. Our findings suggested that these genes are closely associated with potato tuber shape and eye depth. Our study identified molecular markers and candidate genes for improving tetraploid potato tuber shape and eye depth and provided ideas and insights for tetraploid potato breeding.
The areca palm (Areca catechu L.) is one of the most economically important palm trees in tropical areas. To inform areca breeding programs, it is critical to characterize the genetic bases of the mechanisms that regulate areca fruit shape and to identify candidate genes related to fruit-shape traits. However, few previous studies have mined candidate genes associated with areca fruit shape. Here, the fruits produced by 137 areca germplasms were divided into three categories (spherical, oval, and columnar) based on the fruit shape index. A total of 45,094 high-quality single-nucleotide polymorphisms (SNPs) were identified across the 137 areca cultivars. Phylogenetic analysis clustered the areca cultivars into four subgroups. A genome-wide association study that used a mixed linear model identified the 200 loci that were the most significantly associated with fruit-shape traits in the germplasms. In addition, 86 candidate genes associated with areca fruit-shape traits were further mined. Among the proteins encoded by these candidate genes were UDP-glucosyltransferase 85A2, the ABA-responsive element binding factor GBF4, E3 ubiquitin-protein ligase SIAH1, and LRR receptor-like serine/threonine-protein kinase ERECTA. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that the gene that encoded UDP-glycosyltransferase, UGT85A2, was significantly upregulated in columnar fruits as compared to spherical and oval fruits. The identification of molecular markers that are closely related to fruit-shape traits not only provides genetic data for areca breeding, but it also provides new insights into the shape formation mechanisms of drupes.
Areca , Fruit , Areca/anatomy & histology , Areca/classification , Areca/genetics , Fruit/anatomy & histology , Fruit/classification , Fruit/genetics , Genome-Wide Association Study , Phenotype , Phylogeny , Plant Breeding , Polymorphism, Single Nucleotide
A novel route for an iron-catalyzed tandem sulfonylation, C(sp2)-H activation, cyclization reaction which uses N-phenyl-N-(prop-2-yn-1-yl)benzenesulfonamide and benzenesulfonohydrazide to synthesize derivatives of (Z)-2-phenyl-4-((phenylsulfonyl)methylene)-3,4-dihydro-2H-benzo[e][1,2]thiazine 1,1-dioxide has been developed. The method features convenient operation and good functional group tolerance. In addition, it employs insensitive and inexpensive FeSO4 as the catalyst and provides a direct approach for the preparation of benzothiazides.
Sapindaceae is an economically important family of Sapindales and includes many fruit crops. The dominant transport and storage form of photoassimilates in higher plants is sucrose. Sucrose transporter proteins play an irreplaceable role in the loading, transportation, unloading, and distribution of sucrose. A few SUT (sugar transporter) family genes have been identified and characterized in various plant species. In this study, 15, 15, and 10 genes were identified in litchi, longan, and rambutan, respectively, via genome-wide screening. These genes were divided into four subgroups based on phylogenetics. Gene duplication analysis suggested these genes underwent potent purifying selection and tandem duplications during evolution. The expression levels of SlSut01 and SlSut08 were significantly increased in the fruits of Sapindaceae members. The homologs of these two genes in longan and rambutan were also highly expressed in the fruits. The expression pattern of SUTs in three organs of the two varieties was also explored. Subcellular colocalization experiments revealed that the proteins encoded by both genes were present in the plasma membrane. This report provides data for the functional study of SUTs in litchi and provides a basis for screening sugar accumulation-related genes in fruits of Sapindaceae.
The nuclear enzymes called poly(ADP-ribose)polymerases (PARPs) are known to catalyze the process of PARylation, which plays a vital role in various cellular functions. They have become important targets for the discovery of novel antitumor drugs since their inhibition can induce significant lethality in tumor cells. Therefore, researchers all over the world have been focusing on developing novel and potent PARP inhibitors for cancer therapy. Studies have shown that PARP inhibitors and other antitumor agents, such as EZH2 and EGFR inhibitors, play a synergistic role in cancer cells. The combined inhibition of PARP and the targets with synergistic effects may provide a rational strategy to improve the effectiveness of current anticancer regimens. In this Perspective, we sum up the recent advance of PARP-targeted agents, including single-target inhibitors/degraders and dual-target inhibitors/degraders, discuss the fundamental theory of developing these dual-target agents, and give insight into the corresponding structure-activity relationships of these agents.
Antineoplastic Agents , Neoplasms , Poly(ADP-ribose) Polymerase Inhibitors , Poly(ADP-ribose) Polymerases , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Neoplasms/enzymology , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Poly(ADP-ribose) Polymerases/metabolism , Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors , ErbB Receptors/antagonists & inhibitors , Humans
A novel route for a SnCl2-promoted tandem reduction, ammonolysis, condensation, and deamination reaction which uses nitrile and 2-nitro-N-phenylbenzenesulfonamide/N-(2-nitrophenyl)benzenesulfonamide to synthesize derivatives of benzothiadiazine/1-(phenylsulfonyl)-1H-benzimidazole has been developed. The method features convenient operation and good functional group tolerance. In addition, it employs unsensitive and inexpensive SnCl2/i-PrOH as the reaction reagent and provides a direct approach for the synthesis of pharmaceutically important targets.
Benzimidazoles , Benzothiadiazines , Deamination
Two new bis-bidentate imidazole-substituted nitronyl nitroxide biradicals, BNITIm-C2 (BNITIm-C2 = 1,1'-(1,2-ethanediyl)bis(1H-imidazole-2-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxy-3-oxide)) and BNITIm-C4 (BNITIm-C4 = 1,1'-(1,4-butanediyl)bis(1H-imidazole-2-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxy-3-oxide)), and two series of lanthanide complexes, namely [(BNITIm-C2)Ln(NO3)3](MeOH) (Ln = Gd (1Gd) and Tb (2Tb)), (BNITIm-C2)Dy(NO3)3 (3Dy) and (BNITIm-C4)[Ln(hfac)3]2(C7H8)2 (Ln = Gd (4Gd), Tb (5Tb) and Dy (6Dy), hfac = hexafluoroacetylacetonate), have been prepared and characterized structurally and magnetically. Single crystal X-ray crystallographic analyses revealed that complexes 1Gd-3Dy exhibit 1D chain structures where the Ln(NO3)3 units are bridged by the BNITIm-C2 bis-bidentate biradical, while complexes 4Gd-6Dy exhibit binuclear structures with two Ln(hfac)3 units bridged by the BNITIm-C4 biradical. The bulky hfac anions prohibit the further coordination of LnIII to another NIT ligand and the formation of a similar 1D chain structure. Due to the very long intra- and intermolecular distances of the spin centers, complexes 1Gd-3Dy can be magnetically regarded as an isolated 2p-4f-2p tri-spin system while complex 4Gd-6Dy can be regarded as an isolated 2p-4f bi-spin system. Magnetic analyses on the two GdIII compounds revealed the ferromagnetic GdIII-NIT interactions and antiferromagnetic NIT-NIT interactions through the GdIII ion in 1Gd. Alternating-current (ac) magnetic susceptibility investigations revealed that complex 5Tb exhibits the typical SMM behavior under a zero dc field while complex 6Dy was proved to be a field-induced SMM. Ab initio calculations were performed on complexes 2Tb and 5Tb to understand their magnetic anisotropy together with their different magnetic dynamics.
Four iron(III) complexes, [Fe(qsal-4-F)2]Y·sol (Hqsal-4-F = 4-fluoro-N-(8-quinolyl)salicylaldimine; Y = NO3-, sol = 0.91MeOH·0.57H2O (1NO3); Y = PF6- (2PF6); Y = BF4- (3BF4); Y = OTf-, sol =1.5MeOH (4OTf)), with a new 4-position substituted qsal type ligand Hqsal-4-F have been synthesized and structurally and magnetically characterized. Complexes 1NO3-3BF4 consist of 1D chains formed by the [Fe(qsal-4-F)2]+ cations connected by π-π and C-H···O interactions, which are further linked by more weak interactions to form 2D layers and 3D networks. On the other hand, complex 4OTf has a structure of nearly isolated 1D column where the [Fe(qsal-4-F)2]+ cations are connected by π-π, C-H···π, and C-F···π interactions. Magnetic studies revealed the occurrence of two-step symmetry-breaking SCO in 1NO3 and two-step gradual SCO in 2PF6. Complex 3BF4 undergoes a gradual SCO, whereas 4OTf remains almost high-spin. The smaller anions tend to stabilize the low-spin state, while larger anions tend to stabilize the high-spin state. In addition, the intermediate spin state of 1NO3 could be thermally trapped by quenching from the high temperature, thereby kinetically suppressing the spin transition to the full low-spin state. This work represents a good example that the position of the substituent and the anions plays critical roles in the preparation of SCO materials with tunable properties.
A novel route involving the metal-promoted tandem nitration and halogenation of N-phenylbenzenesulfonamide to synthesize N-(4-halo-2-nitrophenyl)benzenesulfonamide derivatives has been developed. The method shows highly practical chemoselective and functional group compatibility. In addition, it employs insensitive and inexpensive Cu(NO3)2·3H2O, Fe(NO3)3·9H2O, and NH4NO3 as the nitration reagents, and it provides a direct approach for the preparation of 4-halo-2-nitroaniline, which is a crucial intermediate for the synthesis of benzimidazoles and quinoxaline derivatives.
Halogenation , Sulfonamides , Molecular Structure , Benzenesulfonamides
3-Alkyl-3-hydroxyoxindoles, a subclass of oxindole products, have antioxidant, neuroprotective, anticancer, and anti-HIV activities. In this study, a green and economical protocol for the synthesis of 3-alkyl-3-hydroxyoxindoles is developed for the first time via α-alkylation-α-hydroxylation of oxindole with benzyl alcohols without using any transition-metal catalysts in yields of 29-93%.
Alcohols , Alkylation , Hydroxylation , Molecular Structure , Oxindoles
Sulfonamides and lipids are widely found in natural products, bioactive substances, and pharmaceuticals. Here, we report N-sulfonylation and esterification of carboxylic acids in an environment-friendly one-pot tandem protocol involving 1,2-dichloroethane (DCE). Moreover, 1,8-diazabicyclo (5.4.0) undec-7-ene was necessary for this reaction as a strong base, which drives the reaction to completion. Although DCE is a very low activity reagent, it acts not only as a solvent but also as a reactant in the reaction. The ß-chloroester contained in the reaction product can be easily dissociated to react with N, S, and O atoms, increasing the possibility for subsequent synthesis.
A novel pH-responsive probe based on an imidazo[1,2-a]indole fluorophore architecture is reported. The probe was highly selective to strongly acidic pH (pKa = 3.56) with high sensitivity and a fast response time (within 30 s). The probe did not demonstrate any fluorescence changes in the presence of interfering metal ions, and it featured excellent reversibility under strongly acidic conditions. The mechanism of detection of the probe was determined to be based on intramolecular charge transfer (ICT) at different pH. The probe was also able to be used for imaging for detecting acidic pH in Saccharomyces cerevisiae.
Fluorescent Dyes , Saccharomyces cerevisiae , HeLa Cells , Humans , Hydrogen-Ion Concentration , Indoles
Polo-like kinases (PLKs) play important roles in regulating multiple aspects of cell cycle and cell proliferation. In many cancer types, PLK family members are often dysregulated, which can lead to uncontrolled cell proliferation and aberrant cell division and has been shown to associate with poor prognosis of cancers. The key roles of PLK kinases in cancers lead to an enhanced interest in them as promising targets for anticancer drug development. In consideration of PLK inhibitors and some other anticancer agents, such as BRD4, EEF2K and Aurora inhibitors, exert synergy effects in cancer cells, dual-targeting of PLK and other cancer-related targets is regarded as an rational and potent strategy to enhance the effectiveness of single-targeting therapy for cancer treatment. This review introduces the PLK family members at first and then focuses on the recent advances of single-target PLK inhibitors and summarizes the corresponding SARs of them. Moreover, we discuss the synergisms between PLK and other anti-tumor targets, and sum up the current dual-target agents based on them.
Antineoplastic Agents/pharmacology , Cell Cycle Proteins/antagonists & inhibitors , Neoplasms/drug therapy , Protein Kinase Inhibitors/pharmacology , Protein Serine-Threonine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins/antagonists & inhibitors , Animals , Antineoplastic Agents/chemistry , Cell Cycle Proteins/metabolism , Humans , Molecular Structure , Neoplasms/metabolism , Protein Kinase Inhibitors/chemistry , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Polo-Like Kinase 1
