Synthesis and in vitro biological evaluation of novel derivatives of Flexicaulin A condensation with amino acid trifluoroacetate

Yu, Ke; Hu, Tianxing; Huo, Jinxing; Yan, Jun-Ke; Wang, Jinyi; Yang, Rui; Xie, Hang; Liu, Ying; Wang, Ni; Zheng, Zijun; Sun, Yu; Du, Jianxiu; Liu, Hong‐Min

doi:10.1016/j.ejmech.2019.111645

Cited by 10 publications

(1 citation statement)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The experimental results show that when the semi-preparative liquid phase was used to directly purify the crude product, the freeze-dried product was a very fluffy floc that was extremely unstable in the air, which made it difficult to use for subsequent characterization and biological experiments. The crude product was salted and the pH was adjusted to 3 with TFA before more than half of the liquid phase was prepared [ 31 , 32 ]. In addition, 0.5% TFA was added to the liquid phase to obtain the pure product as a powder, flake, or needle solid.…”

Section: Resultsmentioning

confidence: 99%

Novel Approaches for the Solid-Phase Synthesis of Dihydroquinazoline-2(1H)-One Derivatives and Biological Evaluation as Potential Anticancer Agents

et al. 2022

View full text Add to dashboard Cite

In the design of antineoplastic drugs, quinazolinone derivatives are often used as small molecule inhibitors for kinases or receptor kinases, such as the EGFR tyrosine kinase inhibitor gefitinib, p38MAP kinase inhibitor DQO-501, and BRD4 protein inhibitor PFI-1. A novel and convenient approach for the solid-phase synthesis of dihydroquinazoline-2(1H)-one derivatives was proposed and 19 different compounds were synthesized. Cytotoxicity tests showed that most of the target compounds had anti-proliferative activity against HepG-2, A2780 and MDA-MB-231 cell lines. Among them, compounds CA1-e and CA1-g had the most potent effect on A2780 cells, with IC50 values of 22.76 and 22.94 μM, respectively. In addition, in an antioxidant assay, the IC50 of CA1-7 was 57.99 μM. According to bioinformatics prediction, ERBB2, SRC, TNF receptor, and AKT1 were predicted to be the key targets and play an essential role in cancer treatment. ADMET prediction suggested 14 of the 19 compounds had good pharmacological properties, i.e., these compounds displayed clinical potential. The correct structure of the final compounds was confirmed based on LC/MS, 1H NMR, and 13C NMR.

show abstract

Section: Resultsmentioning

confidence: 99%