Abstract

In our continuing search for new anticancer agents, herein we report the synthesis of 2-(4-chloro-3-methylphenoxy)-N'-[(aryl)methylidene]acetohydrazides 3a–j and the evaluation of their anticancer activities on cell viability, morphological changes and caspase-3 activity in cancer cell lines including gastric cancer (MKN45), cervical cancer (HeLa) and breast cancer (MDA-MB-231) cells. 2-(4-chloro-3-methylphenoxy)-N'-[(4-phenylthiophen-2-yl)methylidene] acetohydrazide 3g presented the strongest growth inhibition against MKN45 gastric cancer cell lines with the IC₅₀ value of 1.471 ± 0.23 μM. Moreover, compounds 3b and 3g showed high potency against the HeLa and MDA-MB-231 cell lines having IC₅₀ in the range of 2.38–9.72 μM. These compounds are more selective for the tested human cancer cells than for the mouse fibroblast cell line (NIH/3T3). As a result of the studies conducted in order to understand the molecular mechanism, compounds 3b and 3g enhanced expression of the caspase-3 pro-apoptotic proteins levels besides caspase-3 gene.

摘要

在我们继续寻找新的抗癌剂的过程中，我们报告了 2-(4-chloro-3-methylphenoxy) -N '-[(芳基)亚甲基]乙酰肼3a-j的合成及其对细胞活力的抗癌活性的评估、癌细胞系包括胃癌 (MKN45)、宫颈癌 (HeLa) 和乳腺癌 (MDA-MB-231) 细胞的形态学变化和 caspase-3 活性。2-(4-chloro-3-methylphenoxy) -N '-[(4-phenylthiophen-2-yl)methylidene] acetohydrazide 3g对 MKN45 胃癌细胞系的生长抑制作用最强，IC ₅₀值为 1.471 ± 0.23 μM . 此外，化合物3b和3g对 HeLa 和 MDA-MB-231 细胞系显示出高效力，IC ₅₀范围为 2.38-9.72 μM。这些化合物对测试的人类癌细胞比对小鼠成纤维细胞系 (NIH/3T3) 更具选择性。作为为了解分子机制而进行的研究的结果，化合物3b和3g增强了除 caspase-3 基因之外的 caspase-3 促凋亡蛋白水平的表达。