TY - JOUR
T1 - An artificial neural network model for predicting the subcellular localization of photosensitisers for photodynamic therapy of solid tumours
AU - Tejedor-Estrada, R.
AU - Nonell, S.
AU - Teixidó, J.
AU - Sagristá, M. L.
AU - Mora, M.
AU - Villanueva, A.
AU - Canete, M.
AU - Stockert, J. C.
PY - 2012/5
Y1 - 2012/5
N2 - Photodynamic therapy (PDT) is a promising modality for the treatment of tumours based on the combined action of a photosensitiser (PS), visible light and molecular oxygen, which generates a local oxidative damage that leads to cell death. The site where the primary photodynamic effect takes place depends on the subcellular localization of the PS and affects the mode of action and efficacy of PDT. It is therefore of prime interest to develop structure-subcellular localization prediction models for a PS from its molecular structure and physicochemical properties. Here we describe such a prediction method for the localization of macrocyclic PSs into cell organelles based on a wide set of physicochemical properties and processed through an artificial neural network (ANN). 128 2Dmolecular descriptors related to lipophilicity/hydrophilicity, charge and structural features were calculated, then reduced to 76 by using Pearson's correlation coefficient, and finally to 5 using Guyon and Elisseeff's algorithm. The localization of 61 PSs was compiled from literature and distributed into 3 possible cell structures (mitochondria, lysosomes and "other organelles"). A non-linear ANN algorithm was used to process the information as a decision tree in order to solve PS-organelle assignment: first to identify PSs with mitochondrial and/or lysosomal localization from the rest, and to classify them in a second stage. This sequential ANN classification method has permitted to distinguish PSs located into two of the most important cell targets: lysosomes and mitochondria. The absence of false negatives in this assignation, combined with the rate of success in predicting PS localization in these organelles, permits the use of this ANN method to perform virtual screenings of drug candidates for PDT.
AB - Photodynamic therapy (PDT) is a promising modality for the treatment of tumours based on the combined action of a photosensitiser (PS), visible light and molecular oxygen, which generates a local oxidative damage that leads to cell death. The site where the primary photodynamic effect takes place depends on the subcellular localization of the PS and affects the mode of action and efficacy of PDT. It is therefore of prime interest to develop structure-subcellular localization prediction models for a PS from its molecular structure and physicochemical properties. Here we describe such a prediction method for the localization of macrocyclic PSs into cell organelles based on a wide set of physicochemical properties and processed through an artificial neural network (ANN). 128 2Dmolecular descriptors related to lipophilicity/hydrophilicity, charge and structural features were calculated, then reduced to 76 by using Pearson's correlation coefficient, and finally to 5 using Guyon and Elisseeff's algorithm. The localization of 61 PSs was compiled from literature and distributed into 3 possible cell structures (mitochondria, lysosomes and "other organelles"). A non-linear ANN algorithm was used to process the information as a decision tree in order to solve PS-organelle assignment: first to identify PSs with mitochondrial and/or lysosomal localization from the rest, and to classify them in a second stage. This sequential ANN classification method has permitted to distinguish PSs located into two of the most important cell targets: lysosomes and mitochondria. The absence of false negatives in this assignation, combined with the rate of success in predicting PS localization in these organelles, permits the use of this ANN method to perform virtual screenings of drug candidates for PDT.
KW - Artificial neural network
KW - Photodynamic therapy
KW - Photosensitisers
KW - Subcellular localization
KW - Tumours
UR - http://www.scopus.com/inward/record.url?scp=84860657458&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000303130200014&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.2174/092986712800269290
DO - 10.2174/092986712800269290
M3 - Article
C2 - 22420336
AN - SCOPUS:84860657458
SN - 0929-8673
VL - 19
SP - 2472
EP - 2482
JO - Current Medicinal Chemistry
JF - Current Medicinal Chemistry
IS - 15
ER -