Therapeutical Chemistry Department, National Research Center, Dokki, Cairo 12622, Egypt.
Department of Molecular Biology, National Research Center, Dokki, Cairo 12622, Egypt.
Future Med Chem. 2018 Jan;10(2):157-181. doi: 10.4155/fmc-2017-0137. Epub 2017 Dec 13.
Synthesis of novel glutathione S-transferases (GSTs) inhibitors constitutes a promising strategy in cancer treatment. Results & methodology: A new set of benzimidazoles clubbed with various heterocycles as GST inhibitors and anticancer agents were synthesized. The biological results proved the potential of the new compounds as GST inhibitors, specifically compounds 7 and 14 which produced more potency than ethacrynic acid by three- and tenfold, respectively. Most compounds exhibited promising cytotoxic activity against breast and colon cancer cell lines. Molecular modeling studies revealed that compounds 7 and 14 showed good binding with the amino acids of the GST protein.
Both compounds 7 and 14 fulfilled the Lipinski's rule of five suggesting them as new promising GST inhibitors and anticancer agents.
合成新型谷胱甘肽 S-转移酶（GSTs）抑制剂是癌症治疗的一种有前途的策略。
我们合成了一组新的苯并咪唑与各种杂环作为 GST 抑制剂和抗癌药物。生物实验结果证明了这些新化合物作为 GST 抑制剂的潜力，特别是化合物 7 和 14，其抑制 GST 的活性比依他尼酸分别高出 3 倍和 10 倍。大多数化合物对乳腺癌和结肠癌细胞系表现出良好的细胞毒性活性。分子模拟研究表明，化合物 7 和 14 与 GST 蛋白的氨基酸具有良好的结合性。
化合物 7 和 14 都符合 Lipinski 的五规则，这表明它们是新的有前途的 GST 抑制剂和抗癌药物。
