Grupo de parasitología molecular (GEPAMOL), Centro de investigaciones Biomédicas, Universidad del Quindío, Colombia.
SCIProt, Dpto. de Ciencia y Tecnología, Universidad Nacional de Quilmes, Sáenz Peña 352, Bernal, Argentina.
Arch Oral Biol. 2018 Nov;95:30-39. doi: 10.1016/j.archoralbio.2018.07.015. Epub 2018 Jul 19.
We performed a homology modeling of the structure of a non-mutated and mutated Ser83→Phe DNA gyrase of Porphyromonas gingivalis. The model presented structural features conserved in type II topoisomerase proteins. We designed and evaluated in silico structural modifications to the core of Moxifloxacin by molecular docking, predicted toxicity and steered molecular dynamics simulations (SMD). Our results suggest that 8D derivative of Moxifloxacin could present a strong inhibitory activity in Porphyromonas gingivalis bacteria that exhibits resistance to some conventional fluoroquinolone drugs. Also, our results suggest that hydrophobic radicals in the hydroxyl group at position 3 of the quinolone core would increase the antibacterial activity of the compound when a reported mutation Ser83→Phe is present in the DNA gyrase protein. In addition, new candidates that could have a higher antibacterial activity compared to Moxifloxacin in non-resistant bacteria are proposed.
我们对未突变和突变的 Porphyromonas gingivalis Ser83→Phe DNA 回旋酶进行了同源建模。该模型呈现出 II 型拓扑异构酶蛋白中保守的结构特征。我们通过分子对接设计并评估了莫西沙星核心结构的改造，预测了毒性，并进行了定向分子动力学模拟（SMD）。我们的结果表明，莫西沙星的 8D 衍生物可能对一些传统氟喹诺酮类药物耐药的 Porphyromonas gingivalis 细菌具有很强的抑制活性。此外，我们的结果表明，当 DNA 回旋酶蛋白中存在报道的突变 Ser83→Phe 时，喹诺酮核心 3 位羟基上的疏基自由基会增加化合物的抗菌活性。此外，还提出了一些新的候选药物，与莫西沙星相比，在非耐药细菌中具有更高的抗菌活性。
