Latest ArticlesThe RAS/mitogen-activated protein kinase (MAPK) pathway disorder induced by the missense mutations in the tyrosine-protein phosphatase non-receptor type 11 (PTPN11) gene which resulted in the non-receptor protein tyrosine phosphatase SHP2 dysfunction has been reported in many lung cancer cases. Moreover, the Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) mutation or deletion triggers multiple signaling pathway dysfunctions including RAS/MAPK, RAS/extracellular-signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), Janus kinase/signal transducers and activators of transcription (JAK/STAT) and Hippo/yes-associated protein (YAP) which affect the expression of growth factors, cytokines and hormones. In recent years, the developing of the small molecule SHP2 inhibitors received a lot of attention. In this review, we summarize the recent years' progresses of the SHP2 inhibitors development for the lung cancer treatment.
In this paper, we demonstrate that modification of anion-transport active 1, 3-bis(benzimidazol-2-yl) benzene with strongly electron-withdrawing trifluoromethyl and nitro groups leads to a dramatic increase in the anionophoric activity, and the activity may be greatly regulated by the curvatures of the liposomes used.
A pair of neolignan enantiomers with an unprecedented carbon skeleton, (+)-/(—)-angelignanine [(+)-/(—)-1], was isolated as minor components of an aqueous extract of the Angelica sinensis root heads (guitou). Their structures were determined by spectroscopic data analysis and the absolute configurations were assigned by the circular dichroism (CD) exciton chirality method as well as electronic CD quantum calculations. The enantiomers represent the first 2, 7'-cyclo-8, 9'-neolignans, of which biosynthetic pathways originating from precursors ferulic acid and coniferyl alcohol is proposed. In an in vivo test, both the enantiomers showed significant hypnotic effects at a dose of 10 mg/kg (i.g.).
Antimalarial chemotherapies endowed with effectiveness against drug-resistant parasites and good safety are urgently required in clinical. Our previous research revealed that clinical phase Ⅱ antitumor drug Quisinostat was a promising antimalarial prototype by inhibiting the activity of Plasmodium falciparum (P. falciparum) histone deacetylase (PfHDAC). Herein, 30 novel spirocyclic linker derivatives were designed and synthesized based on Quisinostat as lead compound, and then their antimalarial activities and cytotoxicity were systematically evaluated. Among them, compounds 8 and 27 could effectively eliminate wild-type and multi-drug resistant P. falciparum parasites, and display weakened cytotoxicity and good metabolic stability. Western blot assay demonstrated that they could inhibit PfHDAC activity like Quisinostat. In addition, both 8 and 27 showed certain antimalarial efficacy in rodent malaria model, and the animal toxicity of 8 was significantly improved compared with Quisinostat. Overall, 8 and 27 were structurally novel PfHDAC inhibitors and provided prospective prototype for further antimalarial drug research.
A novel good water-soluble macrocycle containing two pyridinium moieties was synthesized in high yield. It could form 1:1 complexes with neutral guests containing naphthalene or phenyl units in water. The water-soluble macrocycle can selectively encapsulate naphthalene to form a 1:1 complex over a variety of polycyclic aromatic hydrocarbons.
Nowadays, the development of triplet-involved materials becomes a hot research topic in solid-state luminescence fields. However, the mechanism of triplet-involved emission still remains some mysteries to conquer. Here, we proposed a new concept of excited-state conformation capture for the constructions of different types of triplet-involved materials. Firstly, excited-state conformation could be trapped by supramolecular chains in crystal and form a new optimum excited-state structure which is different from that in solution or simple rigid environment, leading to bright thermally activated delayed fluorescence (TADF) emission. Based on excited-state conformation capture methodology, next, we obtained room-temperature phosphorescence (RTP) by introducing Br atoms for the enhancement of intersystem crossing. It could be concluded from experimental results that TADF may originate from aggregate effect while RTP may derive from monomers. Finally, heavy-atom free RTP and ultra RTP were achieved by eliminating aggregate effect. This work could not only extend the design methodology of triplet-involved materials but also set clear evidences for the mechanism of triplet-involved emissions.
Polypeptoids have been explored as mimics of polypeptides, owing to polypeptoids' superior stability upon proteolysis. Polypeptoids can be synthesized from one-pot ring-opening polymerization of amino acid N-substituted N-carboxyanhydrides (NNCAs). However, the speed of polymerization of NNCAs can be very slow, especially for NNCAs bearing a bulky N-substitution group. This hindered the exploration on polypeptoids with more diverse structures and functions. Therefore, it is in great need to develop advanced strategies that can accelerate the polymerization on inactive NNCAs. Hereby, we report that lithium/sodium/potassium hexamethyldisilazide (Li/Na/KHMDS) initiates a substantially faster poly-merization on NNCAs than do commonly used amine initiators, especially for NNCAs with bulky N-substitution group. This fast NNCA polymerization will increase the structure diversity and application of polypeptoids as synthetic mimics of polypeptides.
An unprecedented tunable hydrophobic effect in self-assembly of a small cationic organic fluorophore (NI-TPy+)-based with aggregation-induced emission (AIE) property was realized in aqueous solution. The amplification of hydrophobicity was found to be significantly dependent upon the increasing aggregates of NI-TPy+, which enabled the study of the hydrophobic binding of chaotropic anions with the Hofmeister series.
A convenient synthetic protocol for the hexasubstituted benzene derivatives was successfully developed by DABCO promoted domino reaction of arylidene malononitrile with two molecules of dialkyl but-2-ynedioates. The domino reaction resulted in tetraalkyl 6-cyano-[1, 1'-biphenyl]-2, 3, 4, 5-tetracarboxylates in good to high yields. This formal [2 + 2 + 2] cycloaddition was believed to proceed with sequential nucleophilic addition, Michael addition, annulation and aromatization processes.
Aggregation-induced emission luminogens (AIEgens) have been used in biomacromolecules detection. Herein, TPE-dC and TPE-dU acted as the nucleoside-based AIEgens sensors in the first case, which can be used to detect ctDNA and rRNA in vitro and light up the nucleus in vivo depending on the intermolecular binding affinity. This AIE process enables the quantitative analysis or visualization of nucleic acids in solution or gels state, respectively. Furthermore, confocal laser scanning microscopy (CLSM) images of L929 cells stained with TPE-dC or TPE-dU clearly shows that nucleoside-based AIEgens bio-probes can pass the cell membranes to reach the cell nucleus, without cytotoxicity at the imaging condition (incubation time > 12 h, and 10 μmol/L of concentration). Since the nucleus is rich in DNA/RNA, fluorescence turn-on mode has a great potential in nucleus imaging and clinical diagnosis.
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