Qikprop v 6

Pharmaceutically relevant principal descriptors for all the compounds (see Table 1) were calculated using the QikProp v.6.8 (Schrödinger Release, 2022 : QikProp, Schrödinger, LLC, New York, NY, 2022). As stated in the manual, QikProp is unable to calculate properties for not neutralizable quaternary ammonium compounds, so we were forced to exclude these compounds from all the analyzed databases. For this reason, 7.39%, 3.14%, 0.20%, 4.13%, 0.61%, 2.97%, 4.62%, and 0.14% of the prepared compounds respectively from MBC v.2016, MBC v.2022, ECBL, DrugBank, ZINC, ChEMBL, approved drug library and NuBBE were excluded. The probability of a false readout in a screening assay was determined by HitDexter3.0 (Stork et al., 2020 (link); Stork et al., 2021 (link)). Similarly, 3.61% and 0.15% of MBC v.2022 and ECBL were not able to be processed. With regard to Veber and Ghose filters, both were calculated with RDKit (Landrum, 2016 ; Bento et al., 2020 (link)). The corresponding measurements and thresholds can be found elsewhere (Ghose et al., 1999 (link); Veber et al., 2002 (link)).

Pharmacokinetics properties were calculated using QikProp v 6.8 (Schrodinger ref) in standard mode, and were used to consider properties of relevance to CNS-activity, as well as to predict oral bioavailability. The FAF-Drugs4 online server (https://fafdrugs4.rpbs.univ-paris-diderot.fr/links, accessed on 17 April 2023) [52 (link)] was also used, which considers potential toxicity problems that include structural alerts.