Tasnim Faria, Hosen Md Eram, Haque Md Enamul, Islam Ariful, Nuryay Mst Naharina, Mawya Jannatul, Akter Najnin, Yesmin Delara, Hossain Md Mosabbir, Rahman Nilima, Mahmudul Hasan B M, Hassan Md Naimul, Islam Md Mahmudul, Khalekuzzaman Md
Department of Microbiology, Shaheed Shamsuzzoha Institute of Biosciences, Affiliated with University of Rajshahi, Rajshahi, Bangladesh.
Department of Biotechnology and Genetic Engineering, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh.
In Silico Pharmacol. 2024 Oct 29;12(2):95. doi: 10.1007/s40203-024-00276-3. eCollection 2024.
(), a common human gut bacterium, is generally harmless but capable of causing infections and contributing to diseases like urinary tract infections, sepsis/meningitis, or diarrheal diseases. Notably, is implicated in developing gallbladder cancer (GBC) either through ascending infection from the gastrointestinal tract or via hematogenous spread. Certain strains are known to produce toxins, such as cytolethal distending toxins (CDTs), that directly contribute to the genetic mutations and cellular abnormalities observed in GBC. Broccoli () is known for its health-promoting properties, including antimicrobial, antioxidant, and immunomodulatory effects, and is rich in essential compounds. Our study investigates the potential of the phytochemicals of to inhibit the CdtB (PDB ID: 2F1N) protein of which plays a significant role in the pathogenesis of GBC. By employing in silico molecular docking, Glucosinolates and Indole-3-carbinol emerged as promising inhibitors, demonstrating strong bonding affinities of -8.95 and - 8.5 Kcal/mol, respectively. The molecular dynamic simulation showed that both compounds maintained stable interaction with CdtB with minimal conformational changes observed in the protein-ligand complexes. Additionally, the ADMET analysis provided evidence for the drug-likeness properties of the lead compounds. Furthermore, the DFT (Density Functional Theory) revealed that Indole-3-carbinol is more chemically stable but less reactive than Glucosinolates, with HOMO-LUMO gaps of 5.14 eV and 4.50 eV, respectively. Finally, the in vitro antibacterial assessment confirmed the inhibitory effect of Glucosinolates and Indole-3-carbinol against through disc diffusion assay with the zone of inhibition 34.25 ± 0.541 and 28.67 ± 0.376 mm compared to the control ciprofloxacin. Our study provides crucial data for developing novel therapeutic agents targeting -associated GBC from the phytochemicals of .
The online version contains supplementary material available at 10.1007/s40203-024-00276-3.
（）是一种常见的人体肠道细菌，通常无害，但能够引发感染并导致诸如尿路感染、败血症/脑膜炎或腹泻病等疾病。值得注意的是，（）通过胃肠道上行感染或血行播散与胆囊癌（GBC）的发生有关。已知某些（）菌株会产生毒素，如细胞致死性膨胀毒素（CDTs），这些毒素直接导致在GBC中观察到的基因突变和细胞异常。西兰花（）以其促进健康的特性而闻名，包括抗菌、抗氧化和免疫调节作用，并且富含必需化合物。我们的研究调查了西兰花的植物化学物质抑制（）的CdtB（蛋白质数据银行ID：2F1N）蛋白的潜力，该蛋白在GBC的发病机制中起重要作用。通过计算机模拟分子对接，硫代葡萄糖苷和吲哚 - 3 - 甲醇成为有前景的抑制剂，分别显示出 - 8.95和 - 8.5千卡/摩尔的强结合亲和力。分子动力学模拟表明，这两种化合物与CdtB保持稳定相互作用，在蛋白质 - 配体复合物中观察到最小的构象变化。此外，ADMET分析为先导化合物的类药物性质提供了证据。此外，密度泛函理论（DFT）表明，吲哚 - 3 - 甲醇比硫代葡萄糖苷在化学上更稳定但反应性更低，其最高占据分子轨道 - 最低未占据分子轨道（HOMO - LUMO）间隙分别为5.14电子伏特和4.50电子伏特。最后，体外抗菌评估通过纸片扩散法证实了硫代葡萄糖苷和吲哚 - 3 - 甲醇对（）的抑制作用，与对照环丙沙星相比，抑菌圈分别为34.25±0.541和28.67±0.376毫米。我们的研究为从西兰花的植物化学物质开发针对与（）相关的GBC的新型治疗药物提供了关键数据。
在线版本包含可在10.1007/s40203 - 024 - 00276 - 3获取的补充材料。
