Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, Viale Benedetto XV n.3, Genova, Italy.
J Enzyme Inhib Med Chem. 2012 Oct;27(5):730-43. doi: 10.3109/14756366.2011.611136. Epub 2011 Oct 21.
Tetrahydro-β-carboline derivatives (THBCs) have been identified as a class of potent Type-5 Phosphodiesterase (PDE5) inhibitors, showing benefits for the treatment of erectile dysfunction and also bearing anticancer properties. A computational strategy based on molecular docking studies, followed by docking-based Comparative Molecular Fields Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA), has been used to elucidate the atomic details of the PDE5/THBC interactions and to identify the most important features impacting the THBC PDE5 inhibitory activity. The final CoMSIA model resulted to be the more predictive, showing r(ncv)(2) = 0.96, r(cv)(2) = 0.688, SEE = 0.248, F = 104.800, and r(2)(pred) = 0.78. The results allowed us to obtain useful information for the design of new THBC analogues, potentially acting as PDE5 inhibitors, and to predict their potency prior to synthesis.
四氢-β-咔啉衍生物（THBCs）已被确定为一类有效的 5 型磷酸二酯酶（PDE5）抑制剂，具有治疗勃起功能障碍的益处，并且具有抗癌特性。基于分子对接研究的计算策略，随后是基于对接的比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA），已被用于阐明 PDE5/THBC 相互作用的原子细节，并确定影响 THBC PDE5 抑制活性的最重要特征。最终的 CoMSIA 模型被证明是更具预测性的模型，其 r(ncv)(2) = 0.96、r(cv)(2) = 0.688、SEE = 0.248、F = 104.800 和 r(2)(pred) = 0.78。这些结果使我们能够获得有关设计新的 THBC 类似物的有用信息，这些类似物可能作为 PDE5 抑制剂发挥作用，并在合成之前预测它们的效力。
