Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Department of Biochemistry, College of Science, King Saud University, P.O. Box 22452, Riyadh 11451, Saudi Arabia.
Cells. 2023 Apr 10;12(8):1120. doi: 10.3390/cells12081120.
One of medicinal chemistry's top priorities is the discovery of new molecules with anticancer potential. Compounds that interact with DNA are an intriguing family of chemotherapeutic medications used to treat cancer. Studies in this area have uncovered a plethora of potential anticancer medicines, such as groove binding, alkylating, and intercalator compounds. The anticancer activity of DNA intercalators (molecules that intercalate between DNA base pairs) has drawn special interest. The current study investigated the promising anticancer drug 1,3,5-Tris(4-carboxyphenyl)benzene (H3BTB) against breast and cervical cancer cell lines. In addition, 1,3,5-Tris(4-carboxyphenyl)benzene binds to DNA by groove binding. The binding of H3BTB to DNA was found to be significant which unwinds the DNA helix. Considerable electrostatic and non-electrostatic contributions were present in the binding's free energy. The cytotoxic potential of H3BTB is effectively demonstrated by the computational study outcomes, which include molecular docking and molecular dynamics (MD) simulations. The minor groove binding for the H3BTB-DNA complex is supported by molecular docking research. This study will promote empirical investigation into the synthesis of metallic and non-metallic H3BTB derivatives and their potential use as bioactive molecules for the treatment of cancer.
医学化学的首要任务之一是发现具有抗癌潜力的新分子。与 DNA 相互作用的化合物是一类用于治疗癌症的有趣的化疗药物。该领域的研究揭示了大量潜在的抗癌药物，如沟结合物、烷化剂和嵌入剂化合物。DNA 嵌入剂（嵌入 DNA 碱基对之间的分子）的抗癌活性引起了特别的关注。本研究调查了有前途的抗癌药物 1,3,5-三(4-羧基苯基)苯（H3BTB）对乳腺癌和宫颈癌细胞系的作用。此外，1,3,5-三(4-羧基苯基)苯通过沟结合与 DNA 结合。研究发现 H3BTB 与 DNA 的结合具有重要意义，它会使 DNA 螺旋解开。在结合自由能中存在相当大的静电和非静电贡献。计算研究结果有效地证明了 H3BTB 的细胞毒性潜力，包括分子对接和分子动力学 (MD) 模拟。分子对接研究支持 H3BTB-DNA 复合物的小沟结合。这项研究将促进对金属和非金属 H3BTB 衍生物的合成及其作为治疗癌症的生物活性分子的潜在用途的实证研究。
