Pharmacognosy, BMC-Biomedical Center, Department of Pharmaceutical Biosciences, Faculty of Pharmacy, Uppsala University, S-75123 Uppsala, Sweden.
Department of Pharmaceutical Biology/Pharmacognosy, Institute of Pharmacy, University of Halle-Wittenberg, D-06120 Halle (Saale), Germany.
Molecules. 2022 Jan 24;27(3):753. doi: 10.3390/molecules27030753.
Bedaquiline is a novel adenosine triphosphate synthase inhibitor anti-tuberculosis drug. Bedaquiline belongs to the class of diarylquinolines, which are antituberculosis drugs that are quite different mechanistically from quinolines and flouroquinolines. The fact that relatively similar chemical drugs produce different mechanisms of action is still not widely understood. To enhance discrimination in favor of bedaquiline, a new approach using eight-score principal component analysis (PCA), provided by a ChemGPS-NP model, is proposed. PCA scores were calculated based on 35 + 1 different physicochemical properties and demonstrated clear differences when compared with other quinolines. The ChemGPS-NP model provided an exceptional 100 compounds nearest to bedaquiline from antituberculosis screening sets (with a cumulative Euclidian distance of 196.83), compared with the different 2Dsimilarity provided by Tanimoto methods (extended connective fingerprints and the Molecular ACCess System, showing 30% and 182% increases in cumulative Euclidian distance, respectively). Potentially similar compounds from publicly available antituberculosis compounds and Maybridge sets, based on bedaquiline's eight-dimensional similarity and different filtrations, were identified too.
贝达喹啉是一种新型的三磷酸腺苷合酶抑制剂抗结核药物。贝达喹啉属于二芳基喹啉类，是一种与喹诺酮类和氟喹诺酮类在机制上有很大不同的抗结核药物。相对相似的化学药物产生不同的作用机制这一事实仍未被广泛理解。为了增强对贝达喹啉的区分，提出了一种使用 ChemGPS-NP 模型的 8 分主成分分析（PCA）的新方法。根据 35+1 种不同的物理化学性质计算 PCA 得分，并与其他喹诺酮类药物进行了比较，显示出明显的差异。与 Tanimoto 方法提供的不同 2D 相似性（扩展连接指纹和分子访问系统）相比，ChemGPS-NP 模型提供了 100 种来自抗结核筛选集的与贝达喹啉最接近的化合物（累积欧几里得距离为 196.83），分别增加了 30%和 182%。还根据贝达喹啉的 8 维相似性和不同的过滤，从公开的抗结核化合物和 Maybridge 集中确定了潜在相似的化合物。
