Synthesis and anticancer activity of geldanamycin derivatives derived from biosynthetically generated metabolites.
A new series of geldanamycin derivatives were synthesized using a semi-synthetic approach involving genetically engineered biosynthetic intermediates. These analogues were then evaluated for anti-proliferation activity in human cancer cell lines, SK-Br3 and SK-Ov3. Most of the synthesized compounds exhibited potent in vitro anti-proliferation activity toward both cell lines. Such compounds potently inhibited the expression of the Hsp90 client protein ErbB2.
Lee
Kyeong
K
Korea Research Institute of Bioscience & Biotechnology, 52 Eoeundong, Yuseonggu, Daejeon, 305-806, Korea. kaylee@kribb.re.kr
Ryu
Jung S
JS
Jin
Yinglan
Y
Kim
Woncheol
W
Kaur
Navneet
N
Chung
Sang J
SJ
Jeon
Yong-Jin
YJ
Park
Joon-Tae
JT
Bang
Ji S
JS
Lee
Hong S
HS
Kim
Tae Y
TY
Lee
Jung J
JJ
Hong
Young-Soo
YS
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016227:Benzoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005818:Genetic Engineering; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D047029:Lactams, Macrocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C001277:geldanamycin