888-80-2Relevant articles and documents
Synthesis and identification of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl as potential Aurora A inhibitors
Sang, Chun-Yan,Qin, Wen-Wen,Zhang, Xiu-Juan,Xu, Yu,Ma, You-Zhen,Wang, Xing-Rong,Hui, Ling,Chen, Shi-Wu
, p. 65 - 78 (2018/11/30)
The Aurora kinases are a family of serine/threonine kinases that interact with components of the mitotic apparatus and serve as potential therapeutic targets in oncology. Herein, we reported a series of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl with selective inhibition of Aurora A in either enzymatic assays or cellular phenotypic assays, and displaying more potent anti-proliferation compared with that of VX-680. The most potent compound 10a forms better interaction with Aurora A than Aurora B in molecular docking. Mechanistic studies revealed that 10a disrupt the spindle formation, block the cell cycle progression in the G2/M phase and induce apoptosis in HeLa cell. These results suggested that the produced series of compounds are potential anticancer agents for further development as selective Aurora A inhibitors.
Identification of new pyrrolo[2,3-d]pyrimidines as potent VEGFR-2 tyrosine kinase inhibitors: Design, synthesis, biological evaluation and molecular modeling
Adel, Mai,Serya, Rabah A.T.,Lasheen, Deena S.,Abouzid, Khaled A.M.
, p. 612 - 629 (2018/09/29)
Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in cancer angiogenesis. In the current study, a series of novel pyrrolo[2,3-d]pyrimidine based-compounds was designed and synthesized as VEGFR-2 inhibitors, in accordance to the structure activity relationship (SAR) studies of known type II VEGFR-2 inhibitors. The newly synthesized compounds were evaluated for their ability to inhibit VEGFR-2 kinase enzyme in vitro. All the tested compounds demonstrated highly potent dose-related VEGFR-2 inhibition with IC50 values in nanomolar range. Among these compounds, pyrrolo[2,3-d]pyrimidine derivatives carrying biaryl urea moieties (12d and 15c) exhibited IC50 values of 11.9 and 13.6 nM respectively. Additionally, most of the newly synthesized final compounds were tested on 60 human cancer cell lines. Docking of these compounds into the inactive conformation of VEGFR-2 was performed which showed comparable binding modes to that of the FDA approved VEGFR-2 kinase inhibitors. These newly discovered potent kinase inhibitors could be considered as potential candidates for the development of new targeted anticancer agent.
Synthesis and in vitro antiproliferative activity of novel pyrazolo[3,4-d]pyrimidine derivatives
Abdou, Nermin S.,Serya, Rabah A. T.,Esmat, Ahmed,Tolba, Mai F.,Ismail, Nasser S. M.,Abouzid, Khaled A. M.
, p. 1518 - 1534 (2015/08/18)
A novel series of pyrazolo[3,4-d]pyrimidine derivatives were designed, synthesized and evaluated for their antiproliferative activity. Among the five compounds selected by NCI, compound 11a showed a distinctive pattern of selectivity on cell line panels and was further screened for a 5-log dose range, where it showed potent antiproliferative activity with median growth inhibition (GI50) equal to 1.71 μM against the CNS cancer SNB-75 cell line. The tested derivative showed remarkably the highest cell growth inhibition against non-small cell lung cancer HOP-62, CNS cancer SNB-75, breast cancer HS578T, and melanoma MALME-3M cell lines. Flow cytometric analysis revealed that compound 11a could significantly induce apoptosis in A549 cells in vitro at low micromolar concentrations. Further investigation showed that compound 11a induced significant cell cycle arrest at G0/G1 phase partly due to its ability to downregulate cyclin D1 and upregulate p27kip1 levels.
