Triazolopyridazine derivatives: Synthesis, cytotoxic evaluation, c-Met kinase activity and molecular docking

被引：7
作者：
Ahmed, Eman M. [1 ]
Khalil, Nadia A. [1 ]
Taher, Azza T. [1 ,2 ]
Refaey, Rana H. [3 ]
Nissan, Yassin M. [3 ,4 ]
机构：
[1] Cairo Univ, Fac Pharm, Pharmaceut Organ Chem Dept, Cairo, Egypt
[2] October 6 Univ, Pharmaceut Organ Chem Dept, Fac Pharm, Giza, Egypt
[3] October Univ Modern Sci & Arts MSA, Pharmaceut Chem Dept, Fac Pharm, Giza, Egypt
[4] Cairo Univ, Pharmaceut Chem Dept, Fac Pharm, Kasr Elini St, Cairo 11562, Egypt
来源：
BIOORGANIC CHEMISTRY | 2019年 / 92卷
关键词：
Triazolopyridazines; Pyridazines; Cytotoxic activity; c-Met kinase; NATIONAL-CANCER-INSTITUTE; HEPATOCYTE GROWTH-FACTOR; DRUG DISCOVERY; INHIBITORS; DESIGN; OPTIMIZATION;
D O I：
10.1016/j.bioorg.2019.103272
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Novel series of some triazolo [4,3-b]pyridazine derivatives were designed and synthesized. All the newly synthesized compounds were evaluated for their cytotoxic activity at 10(-5) M concentration towards 60 cancer cell lines according to USA NCI protocol. Most of the synthesized compounds showed good activity against SR (leukemia) cell panel. The most active compounds, 2f and 4a were subjected for further evaluation at a five dose level screening and their efficacy for c-Met kinase inhibition was determined in vitro. Binding mode of these derivatives was explored via molecular docking.
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页数：9
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