J. Braz. Chem. Soc., Vol. 26, No. 6, S1-S38, 2015. Printed in Brazil - ©2015 Sociedade Brasileira de Química Supplementary Information 0103 - 5053 $6.00+0.00 SI In silico Antibacterial Activity Modeling Based on the TOMOCOMD-CARDD Approach Juan A. Castillo-Garit,a,b,c Yovani Marrero-Ponce,b,c,d,e Stephen J. Barigye,*,f Ricardo Medina-Marrero,b,g Milagros G. Bernal,b,g José M. G. de la Vega,h Francisco Torrens,c Vicente J. Arán,i Facundo Pérez-Giménez,d Ramón García-Domenechd and Rosa Acevedo-Barriose aCentro de Estudio de Química Aplicada, Facultad de Química-Farmacia, Universidad Central “Marta Abreu” de Las Villas, 54830 Santa Clara, Villa Clara, Cuba bComputer-Aided Molecular “Biosilico” Discovery and Bioinformatic Research International Network (CAMD-BIR International Network), Los Laureles L76MD, Nuevo Bosque, 130015 Cartagena de Indias, Bolivar, Colombia cInstitut Universitari de Ciència Molecular, Universitat de València, Edifici d’Instituts de Paterna, Poligon la Coma s/n, E-46980, Paterna, Spain dUnidad de Investigación de Diseño de Fármacos y Conectividad Molecular, Departamento de Química Física, Facultad de Farmacia, Universitat de València, 46100 València, Spain eGrupo de Investigación en Estudios Químicos y Biológicos, Facultad de Ciencias Básicas, Universidad Tecnológica de Bolívar, 130010 Cartagena de Indias-Bolívar, Colombia fDepartamento de Química, Universidade Federal de Lavras, 3037, 37200-000 Lavras-MG, Brazil gChemical Bioactive Center, Department of Microbiology, Central University of Las Villas, 54830, Santa Clara-Villa Clara, Cuba hDepartamento de Química Física Aplicada, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049, Madrid, Spain iInstituto de Química Médica, CSIC, c/ Juan de la Cierva 3, 28006, Madrid, Spain Table S1. Random, but not exhaustive, sample of the molecular families of antibacterial agents studied here *e-mail: [email protected] S2 In silico Antibacterial Activity Modeling Based on the TOMOCOMD-CARDD Approach J. Braz. Chem. Soc. Table S2. Results of the classification of active compounds in the training sets Active compounds DP% a Active compounds DP% a name Non-stoc. Stoc. name Non-stoc. Stoc. Mefuralazine 50.55 77.87 Pentisomicin 78.24 71.98 Cryptargol 18.44 –8.10 Betamicin sulfate 88.37 83.59 Arsylen –32.88 –82.20 Argenti fluoresceinas –25.12 –29.86 Fosfomycin –51.44 –23.58 Ftalil-medeyol 86.95 82.49 Taurultam 3.39 –23.00 Nidulin 5.56 28.02 Emimycin –36.72 –37.87 Chloramphenicol monocinnamate 55.98 74.62 Mepartricin A 99.59 99.12 Cefalonium 84.78 87.40 Azaserine 11.66 24.76 Thiatetracycline 61.92 56.92 Nibroxane –17.37 –2.44 Cefodizine 99.30 99.38 Phosphinothricin –25.52 –7.91 Solupyridine 99.64 98.96 Furidiazina 43.63 69.20 Ceforanide 97.35 98.54 Fluoramphenicol 24.29 44.81 Vanyldisulfamide 97.55 92.13 F-8 40.10 59.97 Cefuroxime axetil 96.86 95.45 Iodosil-tabl 48.81 33.65 Butampicillin 42.20 49.77 Furaguanidine 30.15 58.34 Azlocillin sodium 91.80 90.11 Protoxyl 13.05 –81.80 Prodigiosin –54.64 –54.58 Sulfanilamide 15.35 –3.11 Annvithrin 12.57 9.45 Bismuth cevitamate –24.17 –25.72 Andrographolide sodium bisulfite 60.92 40.22 Docitrol 23.37 13.04 Etisomicin 78.11 79.47 Parabortine 21.67 45.96 Micronomicin 75.10 56.46 Allicin –83.43 –43.61 Nitrocefin 92.37 97.93 Diamide –15.16 –49.56 Cefoxazole 85.10 90.67 Cupri gluconas –2.21 –7.20 Sodium diphenicillin 23.37 29.21 Desderman –12.29 9.67 Demecloxycline 70.85 68.26 Dibromsalicylamide –17.09 –5.16 Furampicillin 57.25 63.99 Demethylthiolutin –49.64 31.05 Fumoxicillin sodium 70.30 76.27 Nifuraldezone 49.78 70.07 Nafcillin sodium 39.73 42.99 Sulcimid 44.53 36.47 Sancycline 48.01 33.01 Nihydrazone –0.11 34.81 Demecycline 62.10 51.13 Planomycin 11.50 13.49 BL-S339 95.65 96.32 Sulfamerazine 56.01 59.24 Palmatine –52.94 –83.05 Sulfathiourea 70.06 56.08 Lenampicillin hydrochloride 85.15 83.71 Sulfacarbamide 63.87 50.84 Aristoplomb 99.78 99.47 Mafenide 12.14 –9.72 Mezlocillin sodium 99.12 98.17 Aldanil 61.65 62.69 Sarmoxicillin 67.34 59.75 Mesulfamide sodium 90.78 75.80 Bacampicillin 84.82 82.10 Sulfaguanidina 63.81 54.33 Aspoxicillin 93.83 91.95 Nifurthiazole 50.61 71.29 Pivmecillinam 52.44 48.66 Nitrofurantoin 50.70 70.61 Bluensomycin 99.09 98.15 Furazolidone 22.09 48.47 Hidroxystreptomycin 99.42 98.93 Sulfathiadiazole 82.10 57.10 Netilmicin sulfate 76.59 68.35 Nifuradene 24.10 52.03 Apramycin 95.16 93.06 Methylacetopyronone –48.73 –48.88 Butirosin 95.57 94.40 Fumigatin –58.01 –64.59 Dihydrodesoxyestreptomycin 98.64 97.55 Spinulosin –41.41 –48.95 Erythromycin acetate 92.63 81.98 Sulfacetamide 41.58 28.49 Propikacin 96.59 95.71 Glycylsulfanilamide 55.92 33.20 Lavendamycin 42.15 60.02 Nidroxyzone 43.98 65.55 Actamycin 77.60 80.64 Sulfaperin 59.01 55.49 Talmetoprim 47.12 22.70 Pentizidone sodium –40.33 –33.22 Cefsulodin sodium 98.45 97.53 Septosil 91.34 78.95 Meclocycline 70.85 68.38 Sulfamethoxydiazine 65.29 58.14 Cetocycline hydrochloride 32.41 43.36 Vol. 26, No. 6, 2015 Castillo-Garit et al. S3 Table S2. Results of the classification of active compounds in the training sets (cont.) Active compounds DP% a Active compounds DP% a name Non-stoc. Stoc. name Non-stoc. Stoc. Rifabutin 95.54 94.15 Timoxicillin sodium 88.79 91.58 Broxyquinoline –83.23 1.58 Fenbenicillin potassium 41.29 46.96 Clioquinol –97.01 –2.66 Ticarcillin cresyl sodium 73.44 78.38 Chloroxine –63.76 –31.84 Forbisen –16.75 –13.73 Diiodohydroxyquinoline –24.38 –23.66 Furbenicillin 91.32 90.92 Korinal –52.09 –17.08 Cefpirome 93.88 94.50 Nitroxoline –38.90 –17.25 Ceftazidime 97.95 98.53 Binoxol –76.43 –77.31 Bromtetracycline 77.93 72.63 Bactofuril 40.65 62.80 Tetracycline 63.23 52.71 Furacril 14.74 60.60 Doxycycline 62.10 50.86 Furalazine 23.08 68.35 Oxytetracycline 73.92 66.53 Captan 30.14 49.10 Dithyral –32.72 –18.97 Phenolsufazole 88.49 51.88 Metioxate hydrochloride 36.01 16.59 Melarsenoxyd 31.78 39.53 W 1889 19.02 23.51 Sulfathiazole 66.72 55.46 Pivampicillin hydrochloride 77.14 72.29 Furazoliumchloride 16.76 41.35 Cefbuperazone sodium 99.74 99.68 Furmethoxadone 23.86 52.32 Penethacilline 33.66 32.79 Aureothricin –56.14 10.67 Pleuromulin –38.70 –40.17 Sulfametrole 67.64 83.23 UTH 31 –56.92 –61.94 Nifurimide 25.63 55.00 Amikacin sulfate 98.18 97.72 Melarsen 84.32 59.18 Butikacin 96.62 95.81 Showdomycin 5.40 3.66 Carfecillin sodium 63.75 64.71 Minimycin 31.28 23.37 Propampicillin 57.25 63.99 Sulgin ASG 77.25 67.86 Sulfamazone sodium 99.35 98.67 Anticapsin –32.92 –33.06 Clomocycline 78.71 73.32 Sulfalene 65.02 57.80 Sulfoxyl-salvarsan 73.07 83.34 Dimethylhomosulfamin 3.94 –31.79 Cefaclomezine 89.03 81.65 Chlorozotocin 60.87 75.69 Piperacillin sodium 94.35 93.48 Negamycin 30.33 13.56 Vaneprim 94.32 85.02 Thiocarbarsone 75.92 23.39 Domigon 54.62 28.34 Chlorquinaldol –64.96 –36.23 Framycetin 98.69 98.44 Tilbroquinol –66.85 –54.29 Neomycin C 98.69 98.44 Tiodonium chloride –23.33 –42.53 Talampicillin hydrochloride 75.77 76.16 Dipyrithione –6.52 48.22 Pirbenicillin sodium 90.01 91.69 Akritoin 50.70 70.60 Galactosulfonum 96.91 96.14 Sulfachlorpyridazine 69.67 66.58 PANS 61.32 47.43 Sulfaclozine sodium 60.27 61.75 Glucosulfone 99.99 99.96 Lavulino-INH –8.88 5.49 Stearylsulfamide 41.58 28.56 Rifordin 93.83 92.54 Cefpiramide sodium 98.82 99.40 Miran 17.55 55.48 Fuzlocillin 97.44 97.83 Sulfiodizole 74.67 77.54 Cefoperazone sodium 99.30 99.46 Mequidox –27.63 –44.03 Formo-sulfamerazine 99.58 99.54 Dioxidine –9.86 –29.12 Glycinemethyltetracycline 89.10 80.63 Sulfamidomaleyl 73.73 57.74 Sultamicillin 98.94 98.38 Amifenozin –15.13 –8.59 Methymycin 15.37 –9.39 Sulfadiazine 47.44 61.75 Neomethymycin 13.54 –11.78 Butarsen –62.85 –77.00 Capreomycin 1A 99.95 99.89 Sulfamoxole 61.55 54.77 Cuprimycin 98.59 92.78 Methylsulfathiazole 64.15 59.28 Carindacillin sodium 63.75 64.71 Sulfamethoxazole 52.74 56.19 Fibracillin 81.37 86.06 Sulfasuccinamide 73.73 56.75 Khinoin –1.47 –16.15 Soluseptamid 80.35 65.07 Plauracin 72.25 73.62 S4 In silico Antibacterial Activity Modeling Based on the TOMOCOMD-CARDD Approach J. Braz. Chem. Soc. Table S2. Results of the classification of active compounds in the training sets (cont.) Active compounds DP% a Active compounds DP% a name Non-stoc. Stoc. name Non-stoc. Stoc. Sulfaethidole 80.80 68.91 Mupirosin 39.21 29.52 Sulfatrozole 68.64 87.42 Kanchanomycin 60.23 55.05 Nifurdazil 37.07 61.09 Disulformin 99.98 99.91 Sch 29482 19.35 30.85 Piroxicillin sodium 99.87 99.85 Cordycepin 23.41 46.14 Rolitetracycline 69.98 55.84 Sulfatroxazole 52.74 56.02 Morphocyclin 76.65 61.15 Sulfafurazole 56.12 42.36 Chloramphenicol palmitate 55.98 74.55 Alfasol 97.25 94.33 Steffimycin 79.72 58.86 Nifurethazone 38.55 43.98 Streptomycin B 99.88 99.77 Bismuti camsilas 6.95 –14.42 Cefpimizole sodium 99.78 99.61 Linatine 38.74 40.28 Prolinomethyltetracycline 88.57 81.55 Cloxiquine acetate –71.26 –43.21 Virginiamycin M1 72.00 70.86 Nifurpyrimidine 4.84 49.11 E 702 99.84 99.92 Nitrofurfurylideneisoniazid 19.07 57.26 Superciclin ‘farmabion’ 81.55 77.87 Sulfatriazine 86.06 77.40 Meglucycline 95.85 92.94 Plumbagin –67.85 –64.40 Pipacycline 83.47 71.74 Nifurvidine –0.15 45.13 Guamecycline hydrochloride 97.70 95.32 Nitrosulfapyridine 61.22 72.43 Amicetin 96.03 92.84 Carbadox 65.53 65.31 Chloramphenicol stearate 55.98 74.55 Nifurmazole 61.66 76.60 Lividomycin 99.69 99.61 Sulfapyridine 36.62 34.77 Luteoskyrin 82.79 87.63 Pyridinin 36.89 40.14 Aklavin 66.79 39.35 Tiogin 58.77 64.93 Apicycline 94.19 89.70 Tevenel 82.40 76.81 Sulfacholazine 85.40 82.48 Sulfadicramide 45.84 12.01 Chloramphenicol stearoylglycolate 80.45 87.62 Sulfathylpyrazole 55.51 38.51 Fusidic acid –11.60 –13.03 m-Methoxythioacetazone