Synthesis and cytotoxic activity of N-(2-diethylamino)ethylcarboxamide and other derivatives of 10H-quindoline |
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Authors: | Chen Junjie Deady Leslie W Kaye Anthony J Finlay Graeme J Baguley Bruce C Denny William A |
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Institution: | Chemistry Department, La Trobe University, Victoria 3086, Australia. |
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Abstract: | A series of mono- and dimeric N-methylquindoline carboxamides were prepared by Friedlander condensation between methyl 2-amino-3-formyl benzoate and 3-acetoxy-1-acetylindoles, followed by exhaustive methylation with methyl iodide to give N-methylquindoline esters. Direct amination of these, or hydrolysis to the acids and amine coupling via intermediate imidazolides gave the desired carboxamides. The compounds were evaluated in a panel of cell lines in culture. The monomeric compounds showed similar structure-activity relationships to the known indeno1,2-b]quinolines, with a 4-methyl group increasing potency several-fold. Bis analogues linked through the carboxamide were more cytotoxic than the corresponding monomers in the human leukemia lines, but N-N linked dimers were generally less potent, except for a tetracationic derivative. The most potent monomeric analogue showed moderate growth delay (ca. 5 days) against sub-cutaneously implanted colon 38 tumors in mice. |
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