Artificial neural networks in prediction of antifungal activity of a series of pyridine derivatives against Candida albicans Adam Buciński a, ⁎, Agnieszka Socha a , Małgorzata Wnuk a , Tomasz Bączek b,c , Alicja Nowaczyk d , Jerzy Krysiński e , Krzysztof Goryński a , Marcin Koba c a Department of Biopharmacy, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, M. Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland b Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gen. J. Hallera 107, 80-416 Gdańsk, Poland c Department of Medicinal Chemistry, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, M. Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland d Department of Organic Chemistry, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, M. Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland e Department of Marketing and Pharmaceutical Law, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, M. Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland abstract article info Article history: Received 27 March 2008 Received in revised form 2 September 2008 Accepted 4 September 2008 Available online 13 September 2008 Keywords: Antifungal activity Artificial neural networks (ANNs) Molecular descriptors Pyridine derivatives Sensitivity analysis Quantitative structure-activity relationships (QSAR) studies of antifungal activity against Candida albicans of a large series of new pyridine derivatives were conducted with the use of artificial neural networks (ANNs). The application of ANNs has been provided with respect to the prediction of antimicrobial potency of new pyridine derivatives based on their structural descriptors generated by calculation chemistry. Antifungal activity against C. albicans has been related to a number of physicochemical and structural parameters of the pyridine derivatives investigated. The activity was expressed as logarithm of the reciprocal of the minimal inhibitory concentrations, log 1/MIC. Molecular descriptors of agents were obtained from structure fragment reference databases and by quantum-chemical calculations combined with molecular modeling. A high correlation resulted between the ANN predicted antifungal activity, log 1/MIC pred , and that one from biological experiments, log 1/MIC exp , for the data used in the testing set of pyridine was obtained with correlation coefficient, R, on the level of 0.9112. Crown Copyright © 2008 Published by Elsevier B.V. All rights reserved. 1. Introduction Cationic surfactants with antibacterial properties have an impor- tant role as a sanitizing and antiseptic agents, as components in cosmetic products and pharmaceutical preparations and as germi- cides and fungicides (Fredel, 1994, Madaan and Tyagi, 2008, Oztekin and Erim, 2005). The most popular cationic surfactants used as disinfectants are benzyl-alkyl-ammonium salts and pyridinium salts (Madaan and Tyagi, 2008, Oztekin and Erim, 2005, Vieira and Carmona-Ribeiro, 2006). Pyridinium salts are effective against number of microorganism. They are used to wound irrigation and to treatment of urological infections (Madaan and Tyagi, 2008). Cetylpyridinium chloride controls supragingival plaque and gingivitis (Aschley et al., 1984, Madaan and Tyagi, 2008). Moreover, it also has direct anti-inflammatory activity and inhibits action on several matrix metalloproteinase proteins which cause inflammation. Pyridine derivatives are used as disinfectants for eating and drinking utensils and food processing equipment. Moreover, their antimicrobial activity has been also employed in dairy industry for sanitization of milk cans and milking machines (Banat et al., 2000, Fredel, 1994). The germicidal activity of alkylpyridinium salts is directly related to there chemical properties. Those properties include a reduction in surface tension and formation of ionic aggregates, which results in changes in conductivity and solubility (Fredel,1994). In the homologous series of long hydrocarbon chain alkylpyridinium compounds, their various biological activity increase progressively with increasing chain length up to critical point, beyond which the compound cease to be active (Balgavy and Devinsky, 1996, Madaan and Tyagi, 2008, Pernak et al., 1994, Weglewski et al., 1991). They are adsorbed on the cell membranes of microorganisms and promote various changes in their cell organization (Fredel, 1994, Madaan and Tyagi, 2008). Alkylpyridinium compounds are active against several bacteria and fungi. They are now known to inhibit sporulation, but they are only static agents for mycobacteria (Fredel, 1994). Species of the yeast genus Saccharomyces are associated with spoilage of soft drinks. It was found that pyridinium compounds had excellent activity against vegetative cells of the genus, but destruction of yeast ascospores was delayed, most notably at lower concentration of compounds (Fredel, 1994, Vieira and Carmona-Ribeiro, 2006). Candida albicans is an opportunistic yeast that normally inhabits the mouth, throat, intestines and genitourinary tract of most humans and is usually considered to be a normal part of the bowel flora. However, it may become pathogenic when there is a disturbance in the balance of flora, or a debilitation of the host from other causes (Korukluoglu et al., 2006). Especially, hospitals are the places of an Journal of Microbiological Methods 76 (2009) 25–29 ⁎ Corresponding author. Tel.: +48 52 585 39 9. E-mail address: kizbiofarmacji@cm.umk.pl (A. Buciński). 0167-7012/$ – see front matter. Crown Copyright © 2008 Published by Elsevier B.V. All rights reserved. doi:10.1016/j.mimet.2008.09.003 Contents lists available at ScienceDirect Journal of Microbiological Methods journal homepage: www.elsevier.com/locate/jmicmeth