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Trush, M.M.* ; Kovalishyn, V.* ; Hodyna, D.* ; Golovchenko, O.V.* ; Chumachenko, S.* ; Tetko, I.V. ; Brovarets, V.S.* ; Metelytsia, L.*

In silico and in vitro studies of a number PILs as new antibacterials against MDR clinical isolate Acinetobacter baumannii.

Chem. Biol. Drug Des. 95, 624-630 (2020)
Postprint DOI PMC
Open Access Green
QSAR analysis of a set of previously synthesized phosphonium ionic liquids (PILs) tested against Gram-negative multidrug-resistant clinical isolate Acinetobacter baumannii was done using the Online Chemical Modeling Environment (OCHEM). To overcome the problem of overfitting due to descriptor selection, fivefold cross-validation with variable selection in each step of the model development was applied. The predictive ability of the classification models was tested by cross-validation, giving balanced accuracies (BA) of 76%-82%. The validation of the models using an external test set proved that the models can be used to predict the activity of newly designed compounds with a reasonable accuracy within the applicability domain (BA = 83%-89%). The models were applied to screen a virtual chemical library with expected activity of compounds against MDR Acinetobacter baumannii. The eighteen most promising compounds were identified, synthesized, and tested. Biological testing of compounds was performed using the disk diffusion method in Mueller-Hinton agar. All tested molecules demonstrated high anti-A. baumannii activity and different toxicity levels. The developed classification SAR models are freely available online at and could be used by scientists for design of new more effective antibiotics.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Acinetobacter Baumanii ; Antibacterial Activity ; Machine Learning ; Ochem ; Phosphonium Ionic Liquids; Antimicrobial Resistance; Phosphonium; Susceptibility; Derivatives; Inhibitors
ISSN (print) / ISBN 1747-0277
e-ISSN 1747-0285
Zeitschrift Chemical biology & drug design
Quellenangaben Band: 95, Heft: 6, Seiten: 624-630 Artikelnummer: , Supplement: ,
Verlag Blackwell
Verlagsort Los Angeles, Calif.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)