Abstract

A series of 21 coumarin hydrazide–hydrazone derivatives were designed, synthesized and evaluated potential cytotoxicity effects at 25 μg/mL for 48 h against liver cancer (HepG2) cell line in vitro. Then, seven out of 21 compounds with % cell viability lower than 60% were selected for evaluation of in vitro anti-proliferative activity against liver cancer (HepG2), breast cancer (SKBR-3) and human colon cancer (Caco-2) cell lines. Among the test compounds, 5g, 6d and 6f showed potent activities against both Hep-G2 and SKBR-3 cell lines. More significantly, compound 6d, having a 4-bromophenyl moiety, exhibited best cytotoxic activity against Hep-G2 cell line with IC₅₀ value of 2.84 ± 0.48 μg/mL which is comparable to the standard doxorubicin (IC₅₀ = 2.11 ± 0.13 μg/mL). In addition, compound 6f, having 4-methoxyphenyl moiety, demonstrated the most potent activity (IC₅₀ = 2.34 ± 0.68 μg/mL) against SKBR-3 cell line on comparison with other tested coumarin hydrazide–hydrazone derivatives. Unfortunately, all test compounds, as well as doxorubicin, showed no cytotoxicity toward drug-resistant cell line, Caco-2. Our preliminary results indicated that coumarin hydrazide–hydrazone derivatives could be exploited as leading structures for further anticancer-drug development.

Graphic abstract

Synthesis of coumarin substituted hydrazide-hydrazone derivatives

中文翻译：

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一些新的香豆素取代的酰肼-hydr衍生物的设计合成和抗增殖活性

摘要

设计，合成和评估了一系列21种香豆素酰肼-hydr衍生物，并在体外以25μg/ mL的浓度评估48 h对肝癌（HepG2）细胞系的潜在细胞毒性作用。然后，从21种化合物中筛选出7种细胞存活率低于60％的化合物，以评估其对肝癌（HepG2），乳腺癌（SKBR-3）和人结肠癌（Caco-2）细胞的体外抗增殖活性线。在测试化合物中，5g，6d和6f对Hep-G2和SKBR-3细胞系均显示出有效的活性。更重要的是，具有4-溴苯基部分的化合物6d对IC ₅₀表现出对Hep-G2细胞系的最佳细胞毒性活性值2.84±0.48μg/ mL，与标准阿霉素相当（IC ₅₀  = 2.11±0.13μg/ mL）。此外， 与其他经测试的香豆素酰肼-hydr衍生物相比，具有4-甲氧基苯基部分的化合物6f对SKBR-3细胞系表现出最强的活性（IC ₅₀ = 2.34±0.68μg/ mL）。不幸的是，所有测试化合物以及阿霉素均未显示出对耐药细胞系Caco-2的细胞毒性。我们的初步结果表明，香豆素酰肼-hydr衍生物可以被用作进一步开发抗癌药物的主要结构。

图形摘要

香豆素取代的酰肼-衍生物的合成