537-47-3Relevant articles and documents
Design, synthesis and anticancer evaluation of novel spirobenzo[h]chromene and spirochromane derivatives with dual EGFR and B-RAF inhibitory activities
Abdelatef, Shaimaa A.,El-Saadi, Mohammed T.,Amin, Noha H.,Abdelazeem, Ahmed H.,Omar, Hany A.,Abdellatif, Khaled R.A.
, p. 567 - 578 (2018)
A novel series of spirobenzo[h]chromene and spirochromane derivatives was designed, synthesized and evaluated as potential anticancer agents against MCF-7 (human breast carcinoma), HT-29 (human colorectal adenocarcinoma) and A549 (human lung carcinoma) cell lines using MTT assay. Eight compounds 7, 8e, 13a-e and 16 showed a better anticancer activity than that of sorafenib, the multi-kinase inhibitor with IC50 values between 1.78 and 5.47 μM or erlotinib with IC50 values over 20 μM. Representative compounds 8e, 13c and 16 were selected for further mechanistic investigation via EGFR, B-RAF and tubulin polymerization assays. Compound 16 was the most potent EGFR inhibitor (IC50 = 1.2 μM), yet compounds 8e, 13c and 16 displayed moderate tubulin polymerization inhibition effects. Molecular docking studies of those compounds revealed their possible binding modes into the active sites of both EGFR and B-RAF kinases. The newly developed compounds represent a therapeutically promising approach for the treatment of different types of cancer.
Design, synthesis, and biological activity of novel semicarbazones as potent Ryanodine receptor1 inhibitors of Alzheimer's disease
Dai, Baozhu,Ma, Xingxing,Tang, Yadong,Xu, Le,Guo, Su,Chen, Xinyan,Lu, Shitong,Wang, Guangjie,Liu, Yajing
, (2020/12/09)
Ryanodine receptors (RyRs) are important ligand-gated Ca2+ channels; their excessive activation leads to Ca2+ leakage in the sarcoplasmic reticulum that may cause neurological diseases. In this study, three series of novel potent RyR1 inhibitors based on dantrolene and bearing semicarbazone and imidazolyl moieties were designed and synthesized, and their biological activity was evaluated. Using a single-cell calcium imaging method, the calcium overload inhibitory activities of 26 target compounds were tested in the R614C cell line, using dantrolene as a positive control. The preliminary investigation showed that compound 12a suppressed Ca2+ release as evidenced by store overload-induced Ca2+release (SOICR) (31.5 ± 0.1%, 77.2 ± 0.1%, 93.7 ± 0.2%) at 0.1 μM, 3 μM and 10 μM, respectively. Docking simulation results showed that compound 12a could bind at the active site of the RyR1 protein. The Morris water-maze test showed that compound 12a significantly improved the cognitive behavior of AD-model mice. Further studies on the structural optimization of this series of derivatives are currently underway in our laboratory.
Sulfonyl-containing thioformylhydrazine derivatives, preparation method and application thereof
-
Paragraph 0054; 0057; 0058, (2019/05/22)
The invention discloses sulfonyl-containing thioformylhydrazine derivatives, a preparation method and application thereof. A structural general formula (I) of the sulfonyl-containing thioformylhydrazine derivatives is as follows, wherein R1 is methyl, ethyl, benzyl, 4-methyl benzyl or 2,4-dichlorobenzyl; R2 is hydrogen atom, 4-chlorine, 4-fluoride, 3-methyl, 3,5-dimethyl or 2,6-dimethyl. The sulfonyl-containing thioformylhydrazine derivatives have excellent resistance to bacterial diseases such as rice bacterial leaf blight bacteria, rice bacterial streak bacteria, citrus canker bacteria and the like, and are simple in structure and relatively stable in compound properties. (Shown in the description).
