Synthesis and cytotoxic activity of N-(2-diethylamino)ethylcarboxamide and other derivatives of 10H-quindoline.
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 indeno[1,2-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.
Chen
Junjie
J
Chemistry Department, La Trobe University, Victoria 3086, Australia.
Deady
Leslie W
LW
Kaye
Anthony J
AJ
Finlay
Graeme J
GJ
Baguley
Bruce C
BC
Denny
William A
WA
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000577:Amides / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009368:Neoplasm Transplantation; D011804:Quinolines; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D000470:Alkaloids; D000577:Amides; D000970:Antineoplastic Agents; D007211:Indoles; D011804:Quinolines; C016712:quindoline