title: Oxadiazole derivatives as a novel class of antimitotic agents: Synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines.
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 microM. Lead analogs caused mitotic arrest of A431 human epidermoid cells and cells derived from multi-drug resistant tumors (10, EC(50)=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.
authors.affiliation: Department of Chemistry, ImClone Systems Incorporated, 180 Varick Street, New York, NY 10014, USA. shawn_ouyang@yahoo.com
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Ouyang
authors.forename: Evgueni L
authors.initials: EL
authors.lastname: Piatnitski
authors.forename: Vatee
authors.initials: V
authors.lastname: Pattaropong
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Chen
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: He
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Kiselyov
authors.forename: Avdhoot
authors.initials: A
authors.lastname: Velankar
authors.forename: Joel
authors.initials: J
authors.lastname: Kawakami
authors.forename: Marc
authors.initials: M
authors.lastname: Labelle
authors.forename: Leon
authors.initials: L
authors.lastname: Smith
authors.forename: Julia
authors.initials: J
authors.lastname: Lohman
authors.forename: Sui Ping
authors.initials: SP
authors.lastname: Lee
authors.forename: Asra
authors.initials: A
authors.lastname: Malikzay
authors.forename: James
authors.initials: J
authors.lastname: Fleming
authors.forename: Jason
authors.initials: J
authors.lastname: Gerlak
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Robin L
authors.initials: RL
authors.lastname: Rosler
authors.forename: Kai
authors.initials: K
authors.lastname: Zhou
authors.forename: Stan
authors.initials: S
authors.lastname: Mitelman
authors.forename: Margarita
authors.initials: M
authors.lastname: Camara
authors.forename: David
authors.initials: D
authors.lastname: Surguladze
authors.forename: Jacqueline F
authors.initials: JF
authors.lastname: Doody
authors.forename: M Carolina
authors.initials: MC
authors.lastname: Tuma
mesh_terms: D000818:Animals; D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000145:classification / Q000494:pharmacology*; D011487:Protein Conformation / Q000187:drug effects; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D050256:Antimitotic Agents; D001704:Biopolymers; D010069:Oxadiazoles; D014404:Tubulin