ABSTRACT
A series of 1-azolylalkyl-4(1H)-quinolones has been synthesized and evaluated for cytotoxic activity both in vitro and in vivo. The effects on cytotoxicity of varying substitution on the quinoline moiety was investigated. The insertion of a 5-amino group proved to be the most effective modification, resulting in a several-fold increase in cytotoxicity in vitro. Previously reported results indicated that the activity of this class of compounds may involve topoisomerase inhibition, but investigation of the current compounds has ruled out this possibility. One compound, 13, showed in vitro cytotoxicity notably superior to Adriamycin, however it demonstrated only slight or no in vivo efficacy depending on the model used.
Subject(s)
Antineoplastic Agents/chemical synthesis , Azoles/chemical synthesis , Quinolones/chemical synthesis , Animals , Antineoplastic Agents/pharmacology , Azoles/pharmacology , Doxorubicin/pharmacology , Drug Screening Assays, Antitumor , Humans , Quinolones/pharmacology , Topoisomerase I Inhibitors , Tumor Cells, Cultured/drug effectsABSTRACT
A series of 4-azolylalkyloxyquinolines and 1-azolylalkyl-4(1H)-quinolones has been synthesized and evaluated for cytotoxicity against various cancer cell lines. 1-Phenyl-1,2,3-triazole and 1-methylpyrazole were found to be the most effective azoles. The length of the alkyl chain was critical, with 8 to 10 carbon atoms being optimal. Several of the compounds were found to be very cytotoxic in vitro towards various cancer cells. Compounds 9o, 10k, and 10r were evaluated in vivo, but were ineffective and exhibited acute general toxicity at higher dosages.
Subject(s)
Antineoplastic Agents/chemistry , Azo Compounds/chemistry , Oxyquinoline/chemistry , Quinolines/chemistry , Animals , Antineoplastic Agents/pharmacology , DNA/chemistry , Drug Screening Assays, Antitumor , Humans , Quinolines/pharmacology , Tumor Cells, Cultured/drug effectsABSTRACT
A series of azolylalkylaminoquinolines and azolylalkylthioquinolines was synthesized and evaluated for cytotoxicity against various cancer cell lines. Structure-activity relationships previously established for azolylalkyloxyquinolines were generally found to apply for the present compounds. The azolylalkylaminoquinolines were found to be more cytotoxic than the corresponding thio compounds. Oxidation of 11a to sulfones 12 and 13 resulted in a reduction of cytotoxicity. Several of the compounds were found to be very cytotoxic in vitro towards different cancer cell lines. Compound 7d, the most cytotoxic in vitro against the P388 cell line in this series, was ineffective in vivo and exhibited significant general toxicity at higher dosages.
