Title of article :
Oxadiazole derivatives as a novel class of antimitotic agents: Synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines
Author/Authors :
Xiaohu Ouyang، نويسنده , , Evgueni L. Piatnitski، نويسنده , , Vatee Pattaropong، نويسنده , , Clara Xiaoling Chen، نويسنده , , Hai-Ying He، نويسنده , , Alexander S. Kiselyov، نويسنده , , Avdhoot Velankar، نويسنده , , Joel Kawakami، نويسنده , , Marc Labelle، نويسنده , , Leon Smith II، نويسنده , , Julia Lohman، نويسنده , , Sui Ping Lee، نويسنده , , Asra Malikzay، نويسنده , , James Fleming، نويسنده , , Jason Gerlak، نويسنده , , Ying Wang، نويسنده , , Robin L. Rosler، نويسنده , , Kai Zhou، نويسنده , , Stan Mitelman، نويسنده , , M. Margarita Camara، نويسنده , , et al.، نويسنده ,
Abstract :
Oxadiazole derivatives were synthesized and evaluated for their ability to inhibit tubulin polymerization and to cause mitotic arrest in tumor cells. The most potent compounds inhibited tubulin polymerization at concentrations below 1 μM. Lead analogs caused mitotic arrest of A431 human epidermoid cells and cells derived from multi-drug resistant tumors (10, EC50 = 7.8 nM). Competition for the colchicine binding site and pharmacokinetic properties of selected potent compounds were also investigated and are reported herein, along with structure–activity relationships for this novel series of antimitotic agents.
Keywords :
4-oxadiazole , Antimitotic agent , Multiple-drug resistance , Tubulin polymerization inhibitor , 1 , 3
