Design, Synthesis, Antimicrobial, and Anticancer Activities of Acridine Thiosemicarbazides Derivatives
Design, Synthesis, Antimicrobial, and Anticancer Activities of Acridine Thiosemicarbazides Derivatives
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吖啶硫代氨基脲衍生物的设计、合成、抗菌和抗癌活性
DOI：
10.3390/molecules24112065
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发表时间：
2019-06-01
期刊：
影响因子：
4.6
通讯作者：
Yan, Zhenshuo
中科院分区：
文献类型：
--
作者：
Chen, Rui;Huo, Lini;Yan, Zhenshuo
背景资料：吖啶和硫脲衍生物具有多种生物活性，包括抗癌和抗菌作用，是药物化学中的重要化合物。然而，文献揭示了与使用吖啶类药物相关的一些副作用。这表明，杂化分子可能会减少副作用，并提高由于协同活性的有益特性。本研究的目的是合成并评价新型吖啶氨基硫脲类化合物的抗癌和抗菌性能。结果：化合物4a ~ 4 e的结构经MS和NMR确证。在抗微生物测定中，化合物4c与其他四种化合物相比表现出强的抗微生物活性。在抗肿瘤实验中，我们观察到化合物4a、4 b、4d和4 e对MT-4细胞系具有高的细胞毒性，其IC 50值分别为18.42 ± 1.18、15.73 ± 0.90、10.96 ± 0.62和11.63 ± 0.11 μM。抗肿瘤作用及相关机制的研究表明，其抗肿瘤活性可能与Topo I抑制活性、细胞凋亡及细胞周期有关。分子对接研究表明，平面萘并稠环和柔性硫脲基团的共同存在，可以促进DNA嵌入和抑制DNA-Topo I活性。结论：本研究结果表明，合理设计目标衍生物作为新型抗菌或抗肿瘤先导化合物是可行的。
Background: Acridine and thiourea derivatives are important compounds in medicinal chemistry due to their diverse biological properties including anticancer and antimicrobial effects. However, literature reveals some side effects associated with use of acridines. It is suggested that hybrid molecules may reduce the side effects and enhance the beneficial properties due to synergistic activity. The objectives of the present study are to synthesize and evaluate the anticancer and antimicrobial properties of new hybrids of acridine thiosemicarbazides derivatives. Results: The structures of the synthesized compounds 4a–4e were elucidated by MS and NMR spectra. In antimicrobial assay, Compound 4c exhibited potent antimicrobial activity compared to the other four compounds. In anticancer studies, we observed that compounds 4a, 4b, 4d and 4e exhibited high cytotoxicity against the MT-4 cell line, with IC50 values of 18.42 ± 1.18, 15.73 ± 0.90, 10.96 ± 0.62 and 11.63 ± 0.11 μM, respectively. The evaluation of anticancer effects, and the associated mechanism reveals that, the anticancer activities may be related to Topo I inhibitory activity, apoptosis and cell-cycle. Molecular docking studies revealed that the presence of planar naphtho-fused rings and a flexible thiourea group together, could improve DNA-intercalation and inhibition of DNA-Topo I activity. Conclusions: The results of this study demonstrate that the rational design of target derivatives as novel antimicrobial or antitumor leads is feasible.