Synthesis and cytotoxic activity of 2-acyl-1H-indole-4,7-diones on human cancer cell lines.
Synthesis and cytotoxic activity of a series of 2-acyl-1H-indole-4,7-diones on human cancer cell lines are described. Due to close structural relationship to 2-acylindoles, potent inhibitors of tubulin polymerization, the mode of action of these novel compounds has been investigated. Cytotoxicity, the influence on tubulin polymerization, and cell cycle dependent cytotoxicity on colon carcinoma cells by investigation of RKO exo p27 versus RKO p27(kip1) cells are described. IC50 values of arrested versus proliferating cells differ only in a range of two to fourfold and therefore cellular targets, predominantly relevant for mitotic progression, are excluded. As shown by the significant difference in the IC90 values on different tumor cell lines, the investigated compounds seem to act selectively on mammary and renal cancer cells.
Mahboobi
Siavosh
S
Department of Pharmaceutical Chemistry I, University of Regensburg, 93040 Regensburg, Germany. siavosh.mahboobi@chemie.uni-regensburg.de
Sellmer
Andreas
A
Eichhorn
Emerich
E
Beckers
Thomas
T
Fiebig
Heinz-Herbert
HH
Kelter
Gerhard
G
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D002417:Cattle; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007659:Ketones / Q000138:chemical synthesis / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; C436291:CDKN1B protein, human; D002352:Carrier Proteins; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D007659:Ketones; D014404:Tubulin; D050760:Cyclin-Dependent Kinase Inhibitor p27