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

Ahmed E.M.; Khalil N.A.; Taher A.T.; Refaey R.H.; Nissan Y.M.

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

Ahmed E.M.; Khalil N.A.; Taher A.T.; Refaey R.H.; Nissan Y.M.

Full Text link: https://t.ly/AXqNp

Date issued: 2019

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Doi: https://doi.org/10.1016/j.bioorg.2019.103272 PubMed ID 31539742

Publisher: Academic Press Inc.

Series Info: Bioorganic Chemistry
92

Type: Article

Keywords: c-Met kinase , Cytotoxic activity , Pyridazines , Triazolopyridazines , cytotoxic agent , phosphotransferase inhibitor , scatter factor receptor , triazolopyridazine derivative , antineoplastic activity , Article , breast cancer , cancer inhibition , central nervous system cancer , colon cancer , controlled study , drug binding , drug efficacy , drug screening , drug synthesis , enzyme activity , enzyme inhibition , GI50 , human , human cell , IC50 , in vitro study , kidney cancer , leukemia , melanoma , molecular docking , non small cell lung cancer , ovary cancer , priority journal , prostate cancer , proton nuclear magnetic resonance , structure activity relation

Abstract:

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. 2019 Elsevier Inc.