title: Synthesis and biological evaluation of 2,4-diaminoquinazoline derivatives as novel heat shock protein 90 inhibitors.
abstract: Novel 2,4-diaminoquinazoline derivatives originating from a virtual screening approach were designed, synthesized and their biological activities as heat shock protein 90 (Hsp90) inhibitors were evaluated. The prepared compounds exhibited significant anti-proliferative activities against DU-145, HT-29, HCT-116, A375P and MCF-7 cancer cell lines. The selected compounds were tested against Her2, a client protein of Hsp90, and showed significant reduction in Her2 protein expression. Compound 6b was found the most potent, reduced Her2 protein expression levels and induced Hsp70 protein expression levels significantly.
authors.affiliation: Neuro-Medicine Center, Korea Institute of Science and Technology, Seoul, Republic of Korea.
authors.forename: Dhanaji Achyutrao
authors.initials: DA
authors.lastname: Thorat
authors.forename: Munikumar Reddy
authors.initials: MR
authors.lastname: Doddareddy
authors.forename: Seon Hee
authors.initials: SH
authors.lastname: Seo
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Hong
authors.forename: Yong Seo
authors.initials: YS
authors.lastname: Cho
authors.forename: Ji-Sook
authors.initials: JS
authors.lastname: Hahn
authors.forename: Ae Nim
authors.initials: AN
authors.lastname: Pae
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D018841:HSP90 Heat-Shock Proteins; D011799:Quinazolines; C013474:2,4-diaminoquinazoline