Docking-based CoMFA and CoMSIA analyses of tetrahydro-β-carboline derivatives as type-5 phosphodiesterase inhibitors.

摘要

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 MolecularFields Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA), has been used to elucidatethe atomic details of the PDE5/THBC interactions and to identify the most important features impacting the THBCPDE5 inhibitory activity. The final CoMSIA model resulted to be the more predictive, showing rncv2 = 0.96, rcv2 = 0.688,SEE = 0.248, F = 104.800, and r2pred = 0.78. The results allowed us to obtain useful information for the design of newTHBC analogues, potentially acting as PDE5 inhibitors, and to predict their potency prior to synthesis