title: Synthesis and biological evaluation of aryloxazole derivatives as antimitotic and vascular-disrupting agents for cancer therapy.
abstract: A series of aryloxazole, thiazole, and isoxazole derivatives was synthesized as vascular-targeting anticancer agents. Antiproliferative activity and tumor vascular-disrupting activity of all of the synthesized compounds were tested in vitro using various human cancer cell lines and HUVECs (human umbilical vein endothelial cells). Several compounds with an arylpiperazinyl oxazole core showed excellent cytotoxicity and metabolic stability in vitro. Among this series, two representative compounds (6-48 and 6-51) were selected and tested for the evaluation of anticancer effects in vivo using tumor-bearing mice. Compound 6-48 effectively reduced tumor growth (42.3% reduction in size) at the dose of 100 mg/kg. We believe that compound 6-48 will serve as a good lead compound for antimitotic and vascular-disrupting agents; further investigation to improve the in vivo efficacy of this series is underway.
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology , P.O. Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Choi
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: No
authors.forename: Dhanaji Achyutrao
authors.initials: DA
authors.lastname: Thorat
authors.forename: Jae Wan
authors.initials: JW
authors.lastname: Jang
authors.forename: Hakkyun
authors.initials: H
authors.lastname: Yang
authors.forename: Jaeick
authors.initials: J
authors.lastname: Lee
authors.forename: Hyunah
authors.initials: H
authors.lastname: Choo
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Chang Sik
authors.initials: CS
authors.lastname: Lee
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Ko
authors.forename: Jiyoun
authors.initials: J
authors.lastname: Lee
authors.forename: Ghilsoo
authors.initials: G
authors.lastname: Nam
authors.forename: Ae Nim
authors.initials: AN
authors.lastname: Pae
mesh_terms: D000818:Animals; D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004355:Drug Stability; D018922:HL-60 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008862:Microsomes, Liver / Q000378:metabolism; D008958:Models, Molecular; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D050256:Antimitotic Agents; D010080:Oxazoles; D014404:Tubulin