Synthesis and antitumor activity evaluation of some pyrrolone and pyridazinone heterocycles derived from 3-((2-oxo-5-(<i>p</i>-tolyl)furan-3(2<i>H</i>)-ylidene)methyl)quinolin-2(1<i>H</i>)-one

The broad spectrum of biological activity of quinoline derivatives coupled with our interest in the chemistry of furanones led us to synthesize a quinoline derivative bearing a 2(3<i>H</i>)-furanone scaffold. This derivative was used as a key starting material for the construction of some pyrrolone, imidazole, and pyridazinone derivatives obtained by reactions with some nitrogen nucleophiles <i>viz</i>. ammonium acetate, benzylamine, 1,2-diaminoethane, and hydrazine hydrate. The hydrazide obtained was condensed with 3-chlorobenzaldehyde, 1,3-diphenyl-1<i>H</i>-pyrazole-4-carbaldehyde, isatin, and dodecanoyl chloride to achieve the corresponding hydrazone and pyrrolone derivatives. Also, the synthesized compounds were evaluated for their <i>in vitro</i> antitumor activity using two cancer cell lines: breast and colon tumors. Some compounds displayed satisfactory activities.喹啉衍生物（quinoline derivatives）具有广泛的生物活性，加之本课题组对呋喃酮类（furanones）化学的研究兴趣，促使我们合成了一种带有2(3H)-呋喃酮骨架的喹啉衍生物。该衍生物作为关键起始原料，用于构建一系列吡咯酮（pyrrolone）、咪唑（imidazole）及哒嗪酮（pyridazinone）衍生物，这些衍生物可通过与若干亲核氮试剂（nitrogen nucleophiles）即乙酸铵（ammonium acetate）、苄胺（benzylamine）、1,2-乙二胺（1,2-diaminoethane）及水合肼（hydrazine hydrate）的反应制得。将所得酰肼（hydrazide）分别与3-氯苯甲醛（3-chlorobenzaldehyde）、1,3-二苯基-1H-吡唑-4-甲醛（1,3-diphenyl-1H-pyrazole-4-carbaldehyde）、靛红（isatin）及十二烷酰氯（dodecanoyl chloride）进行缩合反应，得到相应的腙（hydrazone）及吡咯酮衍生物。此外，采用乳腺癌细胞系与结肠癌细胞系对所合成的化合物进行了体外（in vitro）抗肿瘤活性评估，部分化合物表现出令人满意的抗肿瘤活性。