Aroyl hydrazones of 2-phenylindole-3-carbaldehydes as novel antimitotic agents.
Cell cycle arrest of malignant cells is an important option for cancer treatment. In this study, we modified the structure of antimitotic 2-phenylindole-3-carbaldehydes by condensation with hydrazides of various benzoic and pyridine carboxylic acids. The resulting hydrazones inhibited the growth of MDA-MB 231 and MCF-7 breast cancer cells with IC(50) values of 20-30 nM for the most potent derivatives. These 2-phenylindole derivatives also exerted an inhibitory effect on the growth of both proliferating and resting U-373 MG glioblastoma cells. Though the hydrazones exhibited similar structure-activity relationships as the aldehydes, they did not inhibit tubulin polymerization as the aldehydes but were capable of blocking the cell cycle in G(2)/M phase. The cell cycle arrest was accompanied by apoptosis as demonstrated by the activation of caspase-3. Since these 2-phenylindole-based hydrazones display no structural similarity with other antitumor drugs they are interesting candidates for further development.
Institut für Pharmazie, Universität Regensburg, D-93040 Regensburg, Germany.
Susanne
S
Vogel
Doris
D
Kaufmann
Michaela
M
Pojarová
Christine
C
Müller
Tobias
T
Pfaller
Sybille
S
Kühne
Patrick J
PJ
Bednarski
Erwin
E
von Angerer
D050256:Antimitotic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001565:Benzoates / Q000737:chemistry; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry
D050256:Antimitotic Agents; D001565:Benzoates; D006835:Hydrazones; D007211:Indoles; D011725:Pyridines; D053148:Caspase 3