Departamento de Química, UEM, Universidade Estadual de Maringá, 87020-900 Maringá, PR, Brazil.
Bioorg Med Chem. 2011 Nov 1;19(21):6400-8. doi: 10.1016/j.bmc.2011.08.059. Epub 2011 Sep 1.
A series of β-carboline derivatives bearing a substituted-carbohydrazide moiety at C-3 were synthesized and evaluated for their antitumor activity against eight human cancer cell lines. The β-carboline N-(substituted-benzylidene)carbohydrazides showed, in general, a greater antitumor activity than their N-(alkylidene)carbohydrazide analogues. The N(9)-methylation of β-carboline N-(substituted-benzylidene) carbohydrazides resulted in a decrease of antitumor activity. Among compounds tested, the benzylidene-carbohydrazides 3, 4, 11, 13, 16, 21 and 22 were the most active, possessing IC(50) less than 10 μM for six of the eight tumor cell lines assayed. The derivative 4 displayed the most significant activity toward all tested cell lines, with a remarkable cytotoxicity against renal (786-0) cell lines (IC(50)=0.04 μM). Compound 4 was assayed for its in vivo antineoplastic activity in the Ehrlich solid carcinoma assay.
一系列在 C-3 位带有取代的碳酰肼部分的β-咔啉衍生物被合成并评估了它们对八种人癌细胞系的抗肿瘤活性。β-咔啉 N-（取代的亚苄基）碳酰肼通常比其 N-（亚烷基）碳酰肼类似物具有更强的抗肿瘤活性。β-咔啉 N-（取代的亚苄基）碳酰肼的 N(9)-甲基化导致抗肿瘤活性降低。在所测试的化合物中，亚苄基碳酰肼 3、4、11、13、16、21 和 22 是最活跃的，对所测试的八种肿瘤细胞系中的六种具有 IC(50)小于 10 μM。衍生物 4 对所有测试的细胞系均表现出最显著的活性，对肾（786-0）细胞系具有显著的细胞毒性（IC(50)=0.04 μM）。化合物 4 在艾氏腹水癌试验中进行了体内抗肿瘤活性的测定。
