Abstract
A data set of 31 benzimidazole derivatives with antibacterial activities against gram-positive (e.g. Staphylococcus aureus, methicillin-resistant S. aureus (MRSA) and Bacillus subtilis) and gram-negative (e.g. Escherichai coli) bacteria as well as antifungal (e.g. Candida albicans) activity were used for quantitative structure–activity relationship (QSAR) study. Compounds were characterized by quantum chemical descriptors calculated at B3LYP/6-31G(d) level and molecular descriptors generated using Dragon software. The QSAR model was constructed using multiple linear regression method and sampled by leave-one-out cross-validation and the predictive performance can be deduced from the correlation coefficient (r), which was in the range of 0.4194–0.8485 while root mean square error (RMSE) was in the range of 0.039–0.3247. Particularly, QSAR model against S. aureus, MRSA (clinical isolates) and E. coli provided good predictive ability with r values of 0.8485, 0.8443 and 0.833, respectively, and RMSE values of 0.2662, 0.2488 and 0.039, respectively. The QSAR models demonstrated high potential for the rational design of novel benzimidazole derivatives with potent antimicrobial activities.
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Achar KC, Hosamani KM, Seetharamareddy HR (2010) In-vivo analgesic and anti-inflammatory activities of newly synthesized benzimidazole derivatives. Eur J Med Chem 45:2048–2054
Becker K, Hu Y, Biller-Andorno N (2006) Infectious diseases–a global challenge. Int J Med Microbiol 296:179–185
Chen JC, Qian L, Shen Y, Zheng KC (2008) A QSAR study and molecular design of benzothiazole derivatives as potent anticancer agents. Sci China Ser B-Chem 58:111–119
Chinedum IE (2005) Microbial resistance to antibiotics. Afr J Biotechnol 4:1606–1611
de Melo EB (2010) Multivariate SAR/QSAR of 3-aryl-4-hydroxyquinolin-2(1H)-one derivatives as type I fatty acid synthase (FAS) inhibitors. Eur J Med Chem 45:5817–5826
de Melo EB, Ferreira MM (2009) Multivariate QSAR study of 4,5-dihydroxypyrimidine carboxamides as HIV-1 integrase inhibitors. Eur J Med Chem 44:3577–3583
Dennington II R, Keith T. Millam J. Eppinnett K, Hovell WL, Gilliland R (2003) GaussView,Version 3.09; Semichem, Inc., Shawnee Mission
Eicher T, Hauptmann S, Speicher A (2004) The chemistry of heterocycles: structure, reactions, syntheses, and applications. Wiley-VCH GmbH & Co. KGaA, Germany
El-masry AH, Fahmy HH, Ali Abdelwahed SH (2000) Synthesis and antimicrobial activity of some new benzimidazole derivatives. Molecules 5:1429–1438
Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas Ö, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009) Gaussian 09, Revision A.1. Wallingford, Connecticut
Isarankura-Na-Ayudhya C, Nantasenamat C, Buraparuangsang P, Piacham T, Ye L, Bülow L, Prachayasittikul V (2008) Computational insights on sulfonamide imprinted polymers. Molecules 13:3077–3091
Kalidhar U, Kaur A (2011) An Overview on some benzimidazole and sulfonamide derivatives with anti-microbial activity. Res J Pharm Biol Chem Sci 2:1116–1135
Karelson M, Lobanov VS, Katritzky AR (1996) Quantum-chemical descriptors in QSAR/QSPR studies. Chem Rev 96:1027–1044
Kuş C, Sözüdönmez F, Can-Eke B, Coban T (2010) Antioxidant and antifungal properties of benzimidazole derivatives. Z Naturforsch C 65:537–542
Low Y, Uehara T, Minowa Y, Yamada H, Ohno Y, Urushidani T, Sedykh A, Muratov E, Kuz’min V, Fourches D, Zhu H, Rusyn I, Tropsha A (2011) Predicting drug-induced hepatotoxicity using QSAR and toxicogenomics approaches. Chem Res Toxicol 24:1251–1262
Nantasenamat C, Naenna T, Isarankura Na-Ayudhya C, Prachayasittikul V (2005) Quantitative prediction of imprinting factor of molecularly imprinted polymers by artificial neural network. J Comput Aided Mol Des 19:509–524
Nantasenamat C, Tantimongcolwat T, Naenna T, Isarankura Na-Ayudhya C, Prachayasittikul (2006) Prediciton of selectivity index of pentachlorophenol-imprinted polymers. EXCLI J 5:150–163
Nantasenamat C, Isarankura-Na-Ayudhya C, Naenna T, Prachayasittikul V (2007a) Quantitative structure-imprinting factor relationship of molecularly imprinted polymers. Biosens Bioelectron 22:3309–3317
Nantasenamat C, Isarankura-Na-Ayudhya C, Tansila N, Naenna T, Prachayasittikul V (2007b) Prediction of GFP spectral properties using artificial neural network. J Comput Chem 28:1275–1289
Nantasenamat C, Isarankura-Na-Ayudhya C, Naenna T, Prachayasittikul V (2008a) Prediction of bond dissociation enthalpy of antioxidant phenols by support vector machine. J Mol Graph Model 27:188–196
Nantasenamat C, Piacham T, Tantimongcolwat T, Naenna T, Isarankura-Na-Ayudhya C, Prachayasittikul V (2008b) QSAR model of the quorum-quenching N-acyl-homoserine lactone lactonase activity. J Biol Syst 16:279–293
Nantasenamat C, Isarankura-Na-Ayudhya C, Naenna T, Prachayasittikul V (2009) A practical overview of quantitative structure-activity relationship. EXCLI J 8:74–88
Nantasenamat C, Isarankura-Na-Ayudhya C, Prachayasittikul V (2010) Advances in computational methods to predict the biological activity of compounds. Exp Opin Drug Discov 5:633–654
Nantasenamat C, Srungboonmee K, Jamsak S, Tansila N, Isarankura-Na-Ayudhya C, Prachayasittikul V (2013) Quantitative structure-property relationship study of spectral properties of green fluorescent protein with support vector machine. Chemometr Intell Lab Syst 120:42–52
Novotarskyi S, Sushko I, Körner R, Pandey AK, Tetko IV (2011) A comparison of different QSAR approaches to modeling CYP450 1A2 inhibition. J Chem Inf Model 51:1271–1280
Nowaczyk A, Kulig K (2012) QSAR studies on a number of pyrrolidin-2-one antiarrhythmic arylpiperazinyls. Med Chem Res 21:373–381
Ozkay Y, Tunalı Y, Karaca H, Işıkdağ I (2011) Antimicrobial activity of a new series of benzimidazole derivatives. Arch Pharm Res 34:1427–1435
Parr RG, Pearson RG (1983) Absolute hardness: companion parameter to absolute electronegativity. J Am Chem Soc 105:7512–7516
Parr RG, Donnelly RA, Levy M, Palke WE (1978) Electronegativity: the density functional viewpoint. J Chem Phys 68:3801–3807
Parr RG, Szentpaly Lv, Liu S (1999) Electrophilicity index. J Am Chem Soc 121:1922–1924
Pasquale G, Romanelli GP, Autino JC, García J, Ortiz EV, Duchowicz PR (2012) Quantitative structure-activity relationships of mosquito larvicidal chalcone derivatives. J Agric Food Chem 60:692–697
Patel JR, Prajapati LM (2012) Predictive QSAR modeling on tetrahydropyrimidine-2-one derivatives as HIV-1 protease enzyme inhibitors. Med Chem Res. doi:10.1007/s00044-012-0275-8
Patil A, Ganguly S, Surana S (2008) A systematic review of benzimidazole derivatives as an antiulcer agent. Rasayan J Chem 3:447–460
Piacham T, Isarankura-Na-Ayudhya C, Nantasenamat C, Yainoy S, Ye L, Bülow L, Prachayasittikul V (2006) Metalloantibiotic Mn(II)-bacitracin complex mimicking manganese superoxide dismutase. Biochem Biophys Res Commun 341:925–930
Piacham T, Nantasenamat C, Suksrichavalit T, Puttipanyalears C, Pissawong T, Maneewas S, Isarankura-Na-Ayudhya C, Prachayasittikul V (2009) Synthesis and theoretical study of molecularly imprinted nanospheres for recognition of tocopherols. Molecules 14:2985–3002
Plata K, Rosato AE, Wegrzyn G (2009) Staphylococcus aureus as an infectious agent: overview of biochemistry and molecular genetics of its pathogenicity. Acta Biochim Pol 56:597–612
Podunavac-Kuzmanovic SO, Cvetkovic DD (2011) QSAR modeling of antibacterial activity of some benzimidazole derivatives. Chem Ind Chem Eng Q 17:33–38
Prachayasittikul V, Isarankura-Na-Ayudhya C, Tantimongcolwat T, Nantasenamat C, Galla HJ (2007) EDTA-induced membrane fluidization and destabilization: biophysical studies on artificial lipid membranes. Acta Biochim Biophys Sin 39:901–913
Prachayasittikul S, Wongsawatkul O, Worachartcheewan A, Nantasenamat C, Ruchirawat S, Prachayasittikul V (2010) Elucidating the structure-activity relationships of the vasorelaxation and antioxidation properties of thionicotinic acid derivatives. Molecules 15:198–214
Refaat HM (2010) Synthesis and anticancer activity of some novel 2-substituted benzimidazole derivatives. Eur J Med Chem 45:2949–2956
Saghaie L, Sakhi H, Hassan Sabzyan H, Shahlaei M, Shamshirian D (2012) Stepwise MLR and PCR QSAR study of the pharmaceutical activities of antimalarial 3-hydroxypyridinone agents using B3LYP/6-311++G** descriptors. Med Chem Res. doi:10.1007/s00044-012-0152-5
Sharma MC, Kohli DV, Sahu NK, Sharma S, Chaturvedi SC (2009) 2D-QSAR studies of some 1,3,4-thidiazole-2yl azetidine 2-one as antimicrobial activity. Dig J Nanomater Bios 4:339–347
Suksrichavalit T, Prachayasittikul S, Piacham T, Isarankura-Na-Ayudhya C, Nantasenamat C, Prachayasittikul V (2008) Copper complexes of nicotinic-aromatic carboxylic acids as superoxide dismutase mimetics. Molecules 13:3040–3056
Suksrichavalit T, Prachayasittikul S, Nantasenamat C, Isarankura-Na-Ayudhya C, Prachayasittikul V (2009) Copper complexes of pyridine derivatives with superoxide scavenging and antimicrobial activities. Eur J Med Chem 44:3259–3265
Thanikaivelan P, Subramanian V, Raghava Rao J, Unni Nair B (2000) Application of quantum chemical descriptor in quantitative structure activity and structure property relationship. Chem Phys Lett 323:59–70
Thippakorn C, Suksrichavalit T, Nantasenamat C, Tantimongcolwat T, Isarankura-Na-Ayudhya C, Naenna T, Prachayasittikul V (2009) Modeling the LPS neutralization activity of anti-endotoxins. Molecules 14:1869–1888
Tuncbilek M, Kiper T, Altanlar N (2009) Synthesis and in vitro antimicrobial activity of some novel substituted benzimidazole derivatives having potent activity against MRSA. Eur J Med Chem 44:1024–1033
Vasanthanathan P, Taboureau O, Oostenbrink C, Vermeulen NP, Olsen L, Jørgensen FS (2009) Classification of cytochrome P450 1A2 inhibitors and noninhibitors by machine learning techniques. Drug Metab Dispos 37:658–664
Walia R, Hedaitullah Md, Naaz SF, Iqbal K, Lamba HS (2011) Benzimidazole derivatives-an overview. IJRPC 1:565–574
Whitley DC, Ford MG, Livingstone DJ (2000) Unsupervised forward selection: a method for eliminating redundant variables. J Chem Inf Comput Sci 40:1160–1168
Witten IH, Frank E, Hall MA (2011) Data mining: practical machine learning tools and techniques, 3rd edn. Morgan Kaufmann, San Francisco
Worachartcheewan A, Nantasenamat C, Naenna T, Isarankura-Na-Ayudhya C, Prachayasittikul V (2009) Modeling the activity of furin inhibitors using artificial neural network. Eur J Med Chem 44:1664–1673
Worachartcheewan A, Prachayasittikul S, Pingaew R, Nantasenamat C, Tantimongcolwat T, Ruchirawat S, Prachayasittikul V (2011a) Antioxidant, cytotoxicity, and QSAR study of 1-adamantylthio derivatives of 3-picoline and phenylpyridines. Med Chem Res 21:3514–3522
Worachartcheewan A, Nantasenamat C, Isarankura-Na-Ayudhya C, Prachayasittikul S, Prachayasittikul V (2011b) Predicting the free radical scavenging activity of curcumin derivatives. Chemometr Intell Lab Syst 109:207–216
Zetola N, Francis JS, Nuermberger EL, Bishai WR (2005) Community-acquired meticillin-resistant Staphylococcus aureus: an emerging threat. Lancet Infect Dis 5:275–286
Zhang L, Zhu H, Oprea TI, Golbraikh A, Tropsha A (2008) QSAR modeling of the blood-brain barrier permeability for diverse organic compounds. Pharm Res 25:1902–1914
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This research project is supported by Office of the Higher Education Commission and Mahidol University under the National Research Universities Initiative.
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Worachartcheewan, A., Nantasenamat, C., Isarankura-Na-Ayudhya, C. et al. Predicting antimicrobial activities of benzimidazole derivatives. Med Chem Res 22, 5418–5430 (2013). https://doi.org/10.1007/s00044-013-0539-y
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DOI: https://doi.org/10.1007/s00044-013-0539-y