Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Department of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Chem Biol Drug Des. 2018 Jan;91(1):220-233. doi: 10.1111/cbdd.13073. Epub 2017 Aug 21.
A series of novel menadione-based triazole hybrids were designed and synthesized by employing copper-catalyzed azide-alkyne cycloaddition (CuAAC). All the synthesized hybrids were characterized by their spectral data ( H NMR, C NMR, IR, and HRMS). The synthesized compounds were evaluated for their anticancer activity against five selected cancer cell lines including lung (A549), prostate (DU-145), cervical (Hela), breast (MCF-7), and mouse melanoma (B-16) using MTT assay. The screening results showed that majority of the synthesized compounds displayed significant anticancer activity. Among the tested compounds, the triazoles 5 and 6 exhibited potent activity against all cell lines. In particular, compound 6 showed higher potency than the standard tamoxifen and parent menadione against MCF-7 cell line. Flow cytometric analysis revealed that compound 6 arrested cell cycle at G0/G1 phase and induced apoptotic cell death which was further confirmed by Hoechst staining, measurement of mitochondrial membrane potential (ΔΨm) and Annexin-V-FITC assay. Thus, compound 6 can be considered as lead molecule for further development as potent anticancer therapeutic agent.
设计并合成了一系列新型基于亚甲二氢醌的三唑杂合化合物，采用铜催化的叠氮-炔环加成（CuAAC）反应。所有合成的杂合化合物均通过其光谱数据（H NMR、C NMR、IR 和 HRMS）进行了表征。采用 MTT 法评估了合成化合物对五种选定的癌细胞系（包括肺癌（A549）、前列腺癌（DU-145）、宫颈癌（Hela）、乳腺癌（MCF-7）和小鼠黑色素瘤（B-16））的抗癌活性。筛选结果表明，大多数合成化合物表现出显著的抗癌活性。在所测试的化合物中，三唑 5 和 6 对所有细胞系均表现出很强的活性。特别是，化合物 6 对 MCF-7 细胞系的活性高于标准他莫昔芬和母体亚甲二氢醌。流式细胞术分析显示，化合物 6 将细胞周期阻滞在 G0/G1 期，并诱导细胞凋亡死亡，这通过 Hoechst 染色、线粒体膜电位（ΔΨm）和 Annexin-V-FITC 测定进一步证实。因此，化合物 6 可被视为进一步开发为有效抗癌治疗剂的潜在先导分子。
