Synthesis and evaluation of a netropsin-proximicin-hybrid library for DNA binding and cytotoxicity.
The proximicins A-C (1-3) are novel naturally occurring gamma-peptides with a hitherto unknown 2,4-disubstituted furan amino acid as a core structure. They show a moderate cytotoxic activity and induce upregulation of cell cycle regulating proteins (p53 and p21) and lead to cell cycle arrest in G0/G1-phase. Hybrid molecules combining structural motifs of the proximicins and of netropsin (4), a structurally related natural product, seem to have similar effects. Herein we describe the synthesis of a netropsin-proximicin-hybrid library and its evaluation regarding cytotoxicity and minor groove binding activity.
FG Organische Chemie, Institut für Chemie, Technische Universität Berlin, Berlin, Germany.
Falko E
FE
Wolter
Lise
L
Molinari
Elke R
ER
Socher
Kathrin
K
Schneider
Graeme
G
Nicholson
Winfried
W
Beil
Oliver
O
Seitz
Roderich D
RD
Süssmuth
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009429:Netropsin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D009429:Netropsin; D004247:DNA