Several dehydroabietylamine derivatives containing heterocyclic moieties such as thiophene and pyrazine ring were successfully synthesized. The antiproliferative activities of these thiophene-based Schiff-bases, thiophene amides, and pyrazine amides were investigated in vitro against Hela (cervix), MCF-7 (breast), A549 (lung), HepG2 (liver), and HUVEC (umbilical vein) cells by MTT assay. The toxicity of L1-L10 (IC50 = 5.92- >100 μM) was lower than L0 (1.27 μM) and DOX (4.40 μM) in every case. Compound L1 had higher anti-HepG2 (0.66 μM), anti-MCF-7 (5.33 μM), and anti-A549 (2.11 μM) and compound L3 had higher anti-HepG2 (1.63 μM) and anti-MCF-7 (2.65 μM) activities. Both of these compounds were recognized with high efficiency in apoptosis induction in HepG2 cells and intercalated binding modes with DNA. Moreover, with average IC50 values of 0.66 and 5.98 μM, L1 was nine times more effective at suppressing cultured HepG2 cells viability than normal cells (SI = 9). The relative tumor proliferation rate (T/C) was 38.6%, the tumor inhibition rate was up to 61.2%, which indicated that L1 had no significant toxicity but high anti-HepG2 activity in vivo. Thus, it may be a potential antiproliferation drug with nontoxic side effects.

中文翻译：

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合成新型 DNA 结合杂环脱氢枞胺衍生物作为潜在的抗增殖和细胞凋亡诱导剂。


成功合成了多种含有噻吩环、吡嗪环等杂环的脱氢枞胺衍生物。在体外研究了这些基于噻吩的席夫碱、噻吩酰胺和吡嗪酰胺对 Hela（子宫颈）、MCF-7（乳房）、A549（肺）、HepG2（肝脏）和 HUVEC（脐静脉）的抗增殖活性）细胞通过MTT测定。在每种情况下，L1-L10 (IC50 = 5.92->100 μM) 的毒性均低于 L0 (1.27 μM) 和 DOX (4.40 μM)。化合物 L1 具有较高的抗 HepG2 (0.66 μM)、抗 MCF-7 (5.33 μM) 和抗 A549 (2.11 μM)，化合物 L3 具有较高的抗 HepG2 (1.63 μM) 和抗 MCF-7 (2.65 μM)。 μM）活动。这两种化合物均能高效诱导 HepG2 细胞凋亡，并具有与 DNA 的嵌入结合模式。此外，L1 的平均 IC50 值为 0.66 和 5.98 μM，抑制培养的 HepG2 细胞活力的效果是正常细胞的九倍 (SI = 9)。相对肿瘤增殖率(T/C)为38.6%，抑瘤率高达61.2%，表明L1在体内无明显毒性，但具有较高的抗HepG2活性。因此，它可能是一种潜在的无毒副作用的抗增殖药物。