Design, Synthesis, and Cytotoxicity of 1H-1,2,3-Triazole Tethered-Benzophenone Based Derivatives as Potent Candidate Anti-Breast Cancer Agents
Design, Synthesis, and Cytotoxicity of 1H-1,2,3-Triazole Tethered-Benzophenone Based Derivatives as Potent Candidate Anti-Breast Cancer Agents
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DOI：
10.1002/slct.202401005
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发表时间：
2024-05-03
期刊：
影响因子：
2.1
通讯作者：
Kanade，Santosh R.
中科院分区：
文献类型：
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作者：
Baka，Durgaprasad;Kishore，Ravada;Kanade，Santosh R.
开发潜在抗癌分子的过程包括谨慎选择核心片段和将具有药理活性的化学功能捆绑到具有生物活性的药效团上。在这里，我们报道了10个1H - 1,2,3 -三唑系链二苯甲酮衍生物的文库。通过我们合成的化合物与一种新的表观遗传癌基因增强子zeste homolog2 （EZH2）的分子对接，进行了蛋白质-配体相互作用的研究。分子对接研究表明，我们合成的化合物对EZH2具有较强的抑制作用，并通过MTT法、台锥蓝染料排除法和体外甲基化试验进行了体外验证，这些研究表明，合成的化合物- 9c、9f、9对EZH2具有较强的抑制作用。在体外检测和分子对接结合研究的支持下，对文库分子对乳腺癌和肺癌（MCF7和A549）细胞系的预期抗癌活性进行了评估。在所有10种化合物中，9c、9f、9c对选定的癌细胞系具有潜在的体外抗癌活性。该结果得到了硅对接研究的支持。体内模型的进一步验证研究将为开发抗乳腺癌和肺癌的有效抑制剂铺平道路。
The process of developing potential anticancer molecules comprises the cautious selection of core moiety and tethering pharmacologically active chemical functionalities to biologically active pharmacophores. Here, we report a library of ten 1H‐1,2,3‐triazole tethered‐benzophenone derivatives. Protein‐ligand interaction studies through molecular docking of our synthesised compounds were carried out with a novel epigenetic oncogene‐enhancer of zeste homolog2 (EZH2). Molecular docking studies disclosed that our synthesized compounds showed potent inhibition against EZH2 andin‐vitrovalidation assays through MTT assay, Trypan blue dye exclusion andin‐vitromethylation assays, these studies revealed the synthesized compounds‐9 c,9 f,9 ishowed potent inhibition on EZH2. The anticipated anti‐cancer activity of library molecules was assessed inin‐vitroagainst breast and lung cancer (MCF7 and A549) cell lines, supported byin‐vitroassays and molecular docking binding studies. Among all ten compounds,9 c,9 f,9 iare exerted potential anti‐cancer activity against the selected cancer cell line inin‐vitro. The results were supported byin‐silicodocking studies. Further validation studies in in‐vivo models will pave a way for developing potent inhibitors against breast cancer and lung cancer.