Synthesis and biological evaluation of novel cytotoxic azanaphthoquinone annelated pyrrolo oximes.
Two series of azanaphthoquinone annelated pyrrolo oximes have been synthesized. The antiproliferative activities of 10 compounds were evaluated on at least four different cell lines. One series of pyrrolo derivatives showed high cytotoxic activity. The effects on cell cycle and caspase activity were investigated. Compounds 9a and 9b showed an accumulation of cells in G2/M phase. Substantial and dose-dependent caspase activity was found after treatment of cells with 9a and 9b. This indicates an apoptosis inducing property of these compounds.
Shanab
Karem
K
Department of Drug and Natural Product Synthesis, University of Vienna, Althanstrasse 14, Vienna, Austria.
Pongprom
Nipawan
N
Wulz
Eva
E
Holzer
Wolfgang
W
Spreitzer
Helmut
H
Schmidt
Peter
P
Aicher
Babette
B
Müller
Gilbert
G
Günther
Eckhard
E
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D008942:Mitoxantrone / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D009285:Naphthoquinones; D010091:Oximes; D011758:Pyrroles; D008942:Mitoxantrone; D020169:Caspases