Prediction of the potential biological activity of novel spiropyrazolo[3,4-b]pyridines and spiropyrazolo[3,4-b]pyridine-5,5'-pyrimidines by a ligand-protein inverse-docking approach

J Mol Graph Model. 2020 Jun;97:107581. doi: 10.1016/j.jmgm.2020.107581. Epub 2020 Mar 12.


The interaction of a series of spiropyrazolo[3,4-b]pyridines and spiropyrazolo[3,4-b]pyridine-5,5'-pyrimidines with 975 molecular targets involved in different diseases and biochemical alterations in humans was assessed. In-silico and in-vivo methods were used to predict the potential biological activity of these compounds. The exposure of several individuals of C. elegans to these compounds shows that their lethality would be less than 10% and that they do not induce any alteration in their locomotion. The compounds identified as PRV-8 and 13-G were the most bioactive, and also showed other advantages such as; better structural properties, adequate pharmacokinetic and pharmacodynamic properties, and good flexibility and unsaturation, which placed them as the compounds of greatest interest to be tested in-vitro and in-vivo. The series of compounds described here exhibited significant interactions with the estrogen signaling pathway.

Keywords: Drug design; Gaussian 09; KEGG Pathway; Molecular docking; Pyrazolopyridines; Pyrazolopyrimidines; String; Sybyl.