Synthesis and Bioevaluation of 3,6-Diaryl-[1,2,4]triazolo[4,3-b] Pyridazines as Antitubulin Agents.

ABSTRACT: A series of 3,6-diaryl-[1,2,4]triazolo[4,3-b]pyridazines were designed as a class of vinylogous CA-4 analogues. The easily isomerized (Z,E)-butadiene linker of vinylogous CA-4 was replaced by a rigid [1,2,4]triazolo[4,3-b]pyridazine scaffold. Twenty-one target compounds were synthesized and exhibited moderate to potent antiproliferative activity. The compound 4q with a 3-amino-4-methoxyphenyl moiety as the B-ring, comparable to CA-4 (IC₅₀ = 0.009-0.012 μM), displayed the highly active antiproliferative activity against SGC-7901, A549, and HT-1080 cell lines with IC₅₀ values of 0.014, 0.008, and 0.012 μM, respectively. Tubulin polymerization experiments indicated that 4q effectively inhibited tubulin polymerization, and immunos

SUBMITTER: Xu Q 

PROVIDER: S-EPMC5150690 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature