Identification of novel and selective anticancer agents remains an important and challenging goal in pharmacological research. In search of new compounds with strong antiproliferative activity and simple molecular structure, we have synthesized three different series of compounds in which different substituents were linked to the 3-amino position of the 2-(3', 4', 5'-trimethoxybenzoyl)-benzo[b]furan or benzo[b]thiophene ring system. These substituents, corresponding to acetyl/haloacetyl, α-bromoacryloyl and nitrooxyacetyl moieties had different electrophilic properties. The benzoheterocycle parent structures were selected because of their reported bioactivities. Compounds bearing a methoxy group at the 6-position of the benzo[b]furan skeleton, were identified as potent antiproliferative agents against the human chronic myelogenous K562 and murine L1210 leukemia cell lines. Comparison of positional isomers indicated that moving the methoxy group from the 6- to the 5- or 7-position yielded inactive compounds. The effects of a selected series of compounds on cell cycle progression correlated well with their strong antiproliferative activity and inhibition of tubulin polymerization. The analysis of structure-activity relationships observed in the series of compounds described here may represent a platform for the design of more active molecules.

中文翻译：

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卤代乙酰基、α-溴丙烯酰基和硝基氧乙酰基苯并 [b] 呋喃和苯并 [b] 噻吩衍生物作为抗白血病 L1210 和 K562 细胞的有效抗增殖剂的合成和评价

鉴定新型和选择性抗癌剂仍然是药理学研究中一个重要且具有挑战性的目标。为了寻找具有强抗增殖活性和简单分子结构的新化合物，我们合成了三个不同系列的化合物，其中不同的取代基连接到 2-(3', 4', 5'-三甲氧基苯甲酰基) 的 3-氨基位置-苯并[b]呋喃或苯并[b]噻吩环系。这些取代基对应于乙酰基/卤代乙酰基、α-溴丙烯酰基和硝基氧乙酰基部分，具有不同的亲电特性。选择苯并杂环母体结构是因为它们具有生物活性。在苯并[b]呋喃骨架的6-位带有甲氧基的化合物，被鉴定为针对人慢性骨髓性 K562 和鼠 L1210 白血病细胞系的有效抗增殖剂。位置异构体的比较表明，将甲氧基从 6- 位移动到 5- 或 7- 位会产生无活性的化合物。选定的一系列化合物对细胞周期进程的影响与其强大的抗增殖活性和微管蛋白聚合的抑制作用密切相关。在此处描述的一系列化合物中观察到的构效关系分析可能代表了设计更活跃分子的平台。选定的一系列化合物对细胞周期进程的影响与其强大的抗增殖活性和微管蛋白聚合的抑制作用密切相关。在此处描述的一系列化合物中观察到的构效关系分析可能代表了设计更活跃分子的平台。选定的一系列化合物对细胞周期进程的影响与其强大的抗增殖活性和微管蛋白聚合的抑制作用密切相关。在此处描述的一系列化合物中观察到的构效关系分析可能代表了设计更活跃分子的平台。