caa a22 4500 445312963 CHVBK 20180317142636.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s11095-010-0317-1 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0317-1 Molecular Interaction Fields (MIFs) to Predict Lipophilicity and ADME Profile of Antitumor Pt(II) Complexes [Elektronische Daten] [Giulia Caron, Mauro Ravera, Giuseppe Ermondi] ABSTRACT: Purpose: To describe a computational tool to calculate molecular descriptors of potential application in ADME virtual screening of antitumor Pt(II) drug candidates. Methods: The multistep computational procedure consists in (a) building and optimization (PM3) of the 3D structures of the investigated complexes, (b) parametrization of Pt(II) and its implementation in GRID, (c) GRID calculations and extraction of the information content with VolSurf and BIOCUBE4mf, and (d) PLS analysis to look for the correlation between experimental data and the molecular descriptors. Results: The following results were obtained: (a) the calibration of the GRID force field to take into account the platinum di-cation, (b) solid PLS models between log k30 and log kw with VolSurf descriptors which highlight the main structural differences between the two chromatographic parameters, (c) the prediction of virtual (of each conformer) log k30 and log kw, and (d) the identification of the main descriptors governing VDss of drugs in clinical use. Conclusion: The study suggests a strategy to identify good Pt(II) complexes prior to their synthesis to eliminate as soon as possible drug candidates with unfavorable PK profile. Springer Science+Business Media, LLC, 2010 ADME prediction nationallicence distribution volume nationallicence lipophilicity nationallicence Molecular Interaction Fields nationallicence Pt(II) complexes nationallicence Caron Giulia CASSMedChem Research Group, DSTF at the Centre for Innovation, Università di Torino, Via Quarello 11, 10135, Torino, Italy aut Ravera Mauro Dipartimento di Scienze dell'Ambiente e della Vita, Università del Piemonte Orientale "Amedeo Avogadro”, Viale Michel 11, 15121, Alessandria, Italy aut Ermondi Giuseppe CASSMedChem Research Group, DSTF at the Centre for Innovation, Università di Torino, Via Quarello 11, 10135, Torino, Italy aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/3(2011-03-01), 640-646 0724-8741 28:3<640 2011 28 11095 https://doi.org/10.1007/s11095-010-0317-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0317-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Caron Giulia CASSMedChem Research Group, DSTF at the Centre for Innovation, Università di Torino, Via Quarello 11, 10135, Torino, Italy aut NATIONALLICENCE 700 1- Ravera Mauro Dipartimento di Scienze dell'Ambiente e della Vita, Università del Piemonte Orientale "Amedeo Avogadro”, Viale Michel 11, 15121, Alessandria, Italy aut NATIONALLICENCE 700 1- Ermondi Giuseppe CASSMedChem Research Group, DSTF at the Centre for Innovation, Università di Torino, Via Quarello 11, 10135, Torino, Italy aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/3(2011-03-01), 640-646 0724-8741 28:3<640 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer