caa a22 4500 445879025 CHVBK 20180317145536.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s11030-010-9274-1 doi (NATIONALLICENCE)springer-10.1007/s11030-010-9274-1 Novel coumarin-based tyrosinase inhibitors discovered by OECD principles-validated QSAR approach from an enlarged, balanced database [Elektronische Daten] [Huong Le-Thi-Thu, Gerardo Casañola-Martín, Yovani Marrero-Ponce, Antonio Rescigno, Luciano Saso, Virinder Parmar, Francisco Torrens, Concepción Abad] The present work is devoted to the development and application of a multi-agent Quantitative Structure-Activity Relationship (QSAR) classification system for tyrosinase inhibitor identification, in which the individual QSAR outputs are the inputs of a fusion approach based on the voting mechanism. The individual models are based on TOMOCOMD-CARDD (TOpological Molecular COMputational Design-Computer Aided Rational Drug Design) atom-based bilinear descriptors and Linear Discriminant Analysis (LDA) on a novel enlarged, balanced database of 1,429 compounds within 701 greatly dissimilar molecules presenting anti-tyrosinase activity. A total of 21 adequate models are obtained taking into account the requirements of the Organization for Economic Cooperation and Development (OECD) principles for QSAR validation and present global accuracies (Q) above 84.50 and 79.27% in the training and test sets, respectively. The resulted fusion system is used for the in silico identification of synthesized coumarin derivatives as novel tyrosinase inhibitors. The 7-hydroxycoumarin (compound C07) shows potent activity for the inhibition of monophenolase activity of mushroom tyrosinase giving a value of inhibition percentage close to 100% in vitro assays, by means of spectrophotometric analysis. The current report could help to shed some clues in the identification of new chemicals that inhibit tyrosinase enzyme, for entering in the pipeline of drug discovery development. Springer Science+Business Media B.V., 2010 Tyrosinase inhibitor nationallicence TOMOCOMD-CARDD software nationallicence Atom-based bilinear index nationallicence Linear discriminant analysis nationallicence QSAR model nationallicence OECD principle nationallicence In silico identification nationallicence In vitro corroboration nationallicence Coumarin nationallicence QSAR : Quantitative structure-activity relationship nationallicence TOMOCOMD-CARDD : Topological molecular computational-design-computer aided rational drug design nationallicence l -DOPA : l-hydroxyphenilalanine nationallicence LDA : Linear discriminant analysis nationallicence HTS : High throughput screening nationallicence OECD : Organization for economic cooperation and development nationallicence Q : Global accuracies nationallicence l -DOPA : l-hydroxyphenilalanine nationallicence AD : Applicability domain nationallicence MD : Molecular descriptor nationallicence NS : Non-stochastic nationallicence SS : Stochastic nationallicence M : Atomic mass nationallicence V : Van der Waals volume nationallicence P : Atomic polarizability nationallicence K : Mulliken electronegativity nationallicence G : Pauling electronegativity nationallicence CA : Cluster analysis nationallicence k -MCA : k-means cluster analysis nationallicence k -NNCA : k-nearest neighbor cluster analysis nationallicence TS : Training set nationallicence PS : Prediction set nationallicence N : Number of compounds nationallicence D 2 : Mahalanobis distance nationallicence R can : The canonical correlation nationallicence χ 2 : The chi-square value nationallicence F : The Fisher ratio nationallicence p (F) : p level nationallicence C : Matthews' correlation coefficient nationallicence TP : True positive nationallicence TN : True negative nationallicence FP : False positive nationallicence FN : False negative nationallicence CV : Cross-validation nationallicence LOO : Leave-one-out nationallicence LMO : Leave-many-out nationallicence LGO : Leave-group-out nationallicence REACH : Registration, evaluation, and authorization of chemicals nationallicence AP : Atomic property nationallicence DF : Discriminant function nationallicence LBVS : Ligand-based virtual screening nationallicence CARDD : Computer-aided-rational drug design nationallicence Le-Thi-Thu Huong Unit of Computer-Aided Molecular ‘Biosilico' Discovery and Bioinformatic Research (CAMD-BIR Unit), Faculty of Chemistry-Pharmacy, Central University of Las Villas, 54830, Santa Clara, Villa Clara, Cuba aut Casañola-Martín Gerardo Unit of Computer-Aided Molecular ‘Biosilico' Discovery and Bioinformatic Research (CAMD-BIR Unit), Faculty of Chemistry-Pharmacy, Central University of Las Villas, 54830, Santa Clara, Villa Clara, Cuba aut Marrero-Ponce Yovani Unit of Computer-Aided Molecular ‘Biosilico' Discovery and Bioinformatic Research (CAMD-BIR Unit), Faculty of Chemistry-Pharmacy, Central University of Las Villas, 54830, Santa Clara, Villa Clara, Cuba aut Rescigno Antonio Dipartimento di Scienze e Tecnologie Biomediche, Università di Cagliari, Cittadella Universitaria, 09042, Monserrato, CA, Italy aut Saso Luciano Department of Physiology and Pharmacology, Sapienza University, Rome, Italy aut Parmar Virinder Department of Chemistry, University of Delhi, Delhi, India aut Torrens Francisco Institut Universitari de Ciència Molecular, Universitat de València, Edifici d'Instituts de Paterna, Poligon la Coma s/n (detras de Canal Nou), P. O. Box 22085, 46071, València, Spain aut Abad Concepción Departament de Bioquímica i Biologia Molecular, Universitat de València, 46100, Burjassot, Spain aut Molecular Diversity Springer Netherlands 15/2(2011-05-01), 507-520 1381-1991 15:2<507 2011 15 11030 https://doi.org/10.1007/s11030-010-9274-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11030-010-9274-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Le-Thi-Thu Huong Unit of Computer-Aided Molecular ‘Biosilico' Discovery and Bioinformatic Research (CAMD-BIR Unit), Faculty of Chemistry-Pharmacy, Central University of Las Villas, 54830, Santa Clara, Villa Clara, Cuba aut NATIONALLICENCE 700 1- Casañola-Martín Gerardo Unit of Computer-Aided Molecular ‘Biosilico' Discovery and Bioinformatic Research (CAMD-BIR Unit), Faculty of Chemistry-Pharmacy, Central University of Las Villas, 54830, Santa Clara, Villa Clara, Cuba aut NATIONALLICENCE 700 1- Marrero-Ponce Yovani Unit of Computer-Aided Molecular ‘Biosilico' Discovery and Bioinformatic Research (CAMD-BIR Unit), Faculty of Chemistry-Pharmacy, Central University of Las Villas, 54830, Santa Clara, Villa Clara, Cuba aut NATIONALLICENCE 700 1- Rescigno Antonio Dipartimento di Scienze e Tecnologie Biomediche, Università di Cagliari, Cittadella Universitaria, 09042, Monserrato, CA, Italy aut NATIONALLICENCE 700 1- Saso Luciano Department of Physiology and Pharmacology, Sapienza University, Rome, Italy aut NATIONALLICENCE 700 1- Parmar Virinder Department of Chemistry, University of Delhi, Delhi, India aut NATIONALLICENCE 700 1- Torrens Francisco Institut Universitari de Ciència Molecular, Universitat de València, Edifici d'Instituts de Paterna, Poligon la Coma s/n (detras de Canal Nou), P. O. Box 22085, 46071, València, Spain aut NATIONALLICENCE 700 1- Abad Concepción Departament de Bioquímica i Biologia Molecular, Universitat de València, 46100, Burjassot, Spain aut NATIONALLICENCE 773 0- Molecular Diversity Springer Netherlands 15/2(2011-05-01), 507-520 1381-1991 15:2<507 2011 15 11030 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer