Chemometric Studies on the Bactericidal Activity of Quinolones via an Extended VolSurf Approach

An extended VolSurf approach, that additionally includes SHAPE descriptors, was applied to a dataset of 55 quinolones. Bactericidal activity was measured at Bayer AG, Germany, for Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis). Chemometric analysis was first approached via a classical VolSurf approach. The following descriptors were found most important:  bactericidal activity particularly increases with high values of the best volume (BV11OH2) and the minimum energy (Emin1OH2) of the water probe, high values of the integy moment (IDDRY) of the lipophilic probe, and high values of the hydrophilic region (WO) of the hydrogen bond acceptor probe. Best volume (BV31OH2) of the water probe and best volume (BV12DRY) and lipophilic regions (DDRY) of the lipophilic probe as well as H-bonding capacity derived with the CO probe (HBO) are inversely related to activity. PLS analysis yields a five-component model with an r2 of 0....