Design, synthesis, and biological evaluation of novel 4‐phenoxypyridine derivatives as potential antitumor agents. Issue 5 (19th March 2019)

• Record Type: Journal Article
• Authors: Liu, Ju; Liu, Yutong; Hao, Xuechen; Wang, Yang; Ji, Jingchao; Liu, Yajing; Ding, Shi; Chen, Ye
• Is Part Of: Archiv der Pharmazie. Volume 352:Issue 5(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-03-19
• Subjects: 4‐phenoxypyridine derivatives -- antitumor activity -- design and synthesis -- VEGFR2 inhibitors; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201800338
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: A series of novel 4‐phenoxypyridine derivatives containing the 4‐oxo‐1, 4‐dihydropyridazine‐3‐carboxamide moiety were synthesized and evaluated for their in vitro cytotoxic activity against the A549 cancer cell line, and some compounds were further examined for their cytotoxic activity against the H460, BGC823, MKN45, and HT‐29 cancer cell lines. Most of the compounds exhibited moderate to significant cytotoxicity. The most promising compound15b (with VEGFR2 inhibitory concentration [IC50 ] value of 0.23 μM) showed remarkable cytotoxicity against A549, BGC‐823, MKN45, H460, and HT‐29 cells, with IC50 values of 0.75, 1.68, 2.63, 5.08 and 7.22 μM, respectively. Their preliminary structure‐activity relationship studies indicate that electron‐withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity. Moreover, treatment of A549 cells with compound15b resulted in cell cycle arrest in the G0 /G1 phase in a dose‐dependent manner. Further apoptotic studies and acridine orange/ethidium bromide staining were also performed on A549 cells, which showed that compound15b could induce apoptosis. Wound‐healing assay results indicated that compound15b strongly inhibited A549 cell motility. Abstract : A series of novel 4‐phenoxypyridine derivatives containing the 4‐oxo‐1, 4‐dihydropyridazine‐3‐carboxamide moiety were synthesized and evaluated for their cytotoxic activities and VEGFR2 kinase activities. Furthermore, cell cycle and apoptotic studies and AO/EB and wound‐healing assay results of compound15b indicated that these compounds deserve further study with regard to their application in the treatment of cancer.