90151-18-1

Upstream product

• 2150-45-0 methyl 2,6-dihydroxybenzoate 
• 54640-04-9 ethyl 2,6-dihydroxybenzoate 
• 303-07-1 2,6-Dihydroxybenzoic acid 

Relevant academic research and scientific papers

Synthesis, photochemical isomerization and photophysical properties of hydrazide-hydrazone derivatives

Hydrazide-hydrazone derivatives have been utilized in molecular switches, sensing, metallo assemblies, drugs and other applications. The hydrazide-hydrazone functional group contains the -CO-NH-NCH- moiety that yields the hydrazide-hydrazone group its physical, chemical and biochemical properties; however, the application in security protection has not been explored before. Herein, the 2-(ortho-), 3-(meta-), 4-(para-) substituted pyridine conjugated to 2,6-dihydroxybenzoic acid, which containing hydrazide-hydrazone as photoswitch linker were designed and synthesized (3a-3c). Interestingly, when irradiating the ortho-substituted pyridine of molecule 3a with a light of 365 nm, obvious emission intensity enhancements were detected. However, 3a-3c before irradiation and 3b-3c after irradiation show no fluorescence. UV-vis, fluorescence, 1H NMR and Fourier transform infrared spectra and density functional theory calculations were carried out, which revealed that the hydrazide-hydrazone derivative of 3a could undergo a characteristic E to Z photoisomerization after light irradiation for 365 nm. The Z isomer of 3a may have additional intramolecular hydrogen bonds to restrict the motions of the molecule, thus increasing the fluorescence intensity of 3a. The experimental and molecular calculation results agreed and thus demonstrated the first example of invisible ink based on the hydrazide-hydrazone motif.

Discovery of an Orally Efficacious MYC Inhibitor for Liver Cancer Using a GNMT-Based High-Throughput Screening System and Structure-Activity Relationship Analysis

Glycine-N-methyl transferase (GNMT) downregulation results in spontaneous hepatocellular carcinoma (HCC). Overexpression of GNMT inhibits the proliferation of liver cancer cell lines and prevents carcinogen-induced HCC, suggesting that GNMT induction is a potential approach for anti-HCC therapy. Herein, we used Huh7 GNMT promoter-driven screening to identify a GNMT inducer. Compound K78 was identified and validated for its induction of GNMT and inhibition of Huh7 cell growth. Subsequently, we employed structure-activity relationship analysis and found a potent GNMT inducer, K117. K117 inhibited Huh7 cell growth in vitro and xenograft in vivo. Oral administration of a dosage of K117 at 10 mpk (milligrams per kilogram) can inhibit Huh7 xenograft in a manner equivalent to the effect of sorafenib at a dosage of 25 mpk. A mechanistic study revealed that K117 is an MYC inhibitor. Ectopic expression of MYC using CMV promoter blocked K117-mediated MYC inhibition and GNMT induction. Overall, K117 is a potential lead compound for HCC- and MYC-dependent cancers.

Hydrazide–Hydrazone Small Molecules as AIEgens: Illuminating Mitochondria in Cancer Cells

Aggregation-induced-emission luminogens (AIEgens) have gained considerable attention as interesting tools for several biomedical applications, especially for bioimaging due to their brightness and photostability. Numerous AIEgens have been developed for lighting up the subcellular organelles to understand their forms and functions not only healthy but also unhealthy states, such as in cancer cells. However, there is lack of easily synthesizable, biocompatible small molecules for illuminating mitochondria (powerhouses) inside cells. To address this issue, an easy and short synthesis of new biocompatible hydrazide–hydrazone-based small molecules with remarkable aggregation-induced emission (AIE) properties is described. These small-molecule AIEgens showed hitherto unobserved AIE properties due to dual intramolecular H-bonding confirmed by theoretical calculation, pH- and temperature-dependent fluorescence and X-ray crystallographic studies. Confocal microscopy showed that these AIEgens were internalized into the HeLa cervical cancer cells without showing any cytotoxicity. One of the AIEgens was tagged with a triphenylphosphine (TPP) moiety, which successfully localized in the mitochondria of HeLa cells in a selective way compared to L929 noncancerous fibroblast cells. These unique hydrazide–hydrazone-based biocompatible AIEgens can serve as powerful tools to illuminate multiple subcellular organelles to elucidate their forms and functions in cancer cells for next-generation biomedical applications.