In order to provide a more detailed view on the structure⁻antimycobacterial activity relationship (SAR) of phenylcarbamic acid derivatives containing two centers of protonation, 1-[2-[({[2-/3-(alkoxy)phenyl]amino}carbonyl)oxy]-3-(dipropylammonio)propyl]pyrrolidinium oxalates (1a⁻d)/dichlorides (1e⁻h) as well as 1-[2-[({[2-/3-(alkoxy)phenyl]amino}carbonyl)oxy]-3-(di-propylammonio)propyl]azepanium oxalates (1i⁻l)/dichlorides (1m⁻p; alkoxy = butoxy to heptyloxy) were physicochemically characterized by estimation of their surface tension (γ; Traube's stalagmometric method), electronic features (log ε; UV/Vis spectrophotometry) and lipophilic properties (log kw; isocratic RP-HPLC) as well. The experimental log kw dataset was studied together with computational logarithms of partition coefficients (log P) generated by various methods based mainly on atomic or combined atomic and fragmental principles. Similarities and differences between the experimental and in silico lipophilicity descriptors were analyzed by unscaled principal component analysis (PCA). The in vitro activity of compounds 1a⁻p was inspected against Mycobacterium tuberculosis CNCTC My 331/88 (identical with H37Rv and ATCC 2794, respectively), M. tuberculosis H37Ra ATCC 25177, M. kansasii CNCTC My 235/80 (identical with ATCC 12478), the M. kansasii 6509/96 clinical isolate, M. kansasii DSM 44162, M. avium CNCTC My 330/80 (identical with ATCC 25291), M. smegmatis ATCC 700084 and M. marinum CAMP 5644, respectively. In vitro susceptibility of the mycobacteria to reference drugs isoniazid, ethambutol, ofloxacin or ciprofloxacin was tested as well. A very unique aspect of the research was that many compounds from the set 1a⁻p were highly efficient almost against all tested mycobacteria. The most promising derivatives showed MIC values varied from 1.9 μM to 8 μM, which were lower compared to those of used standards, especially if concerning ability to fight M. tuberculosis H37Ra ATCC 25177, M. kansasii DSM 44162 or M. avium CNCTC My 330/80. Current in vitro biological assays and systematic SAR studies based on PCA approach as well as fitting procedures, which were supported by relevant statistical descriptors, proved that the compounds 1a⁻p represented a very promising molecular framework for development of 'non-traditional' but effective antimycobacterial agents.

Clinic for Department of Infectious Diseases and Microbiology Faculty of Veterinary Medicine University of Veterinary and Pharmaceutical Sciences Palackého 1946 1 CZ 612 42 Brno Czech Republic

Clinic for Tuberculosis and Lung Diseases National Institute for Tuberculosis Lung Diseases and Thoracic Surgery Vyšné Hágy SK 059 84 Vysoké Tatry Slovakia

Department of Chemical Drugs Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences in Brno Palackého 1946 1 CZ 612 42 Brno Czech Republic

Department of Pharmaceutical Analysis and Nuclear Pharmacy Faculty of Pharmacy Comenius University in Bratislava Odbojárov 10 SK 832 32 Bratislava Slovakia

Department of Pharmaceutical Chemistry Faculty of Pharmacy Comenius University in Bratislava Odbojárov 10 SK 832 32 Bratislava Slovakia

Department of Public Health Faculty of Health Catholic University in Ružomberok Hrabovská cesta 1A SK 034 01 Ružomberok Slovakia

Global Change Research Institute CAS Belidla 986 4a CZ 603 00 Brno Czech Republic

Laboratory for Mycobacterial Diagnostics and Tuberculosis Regional Institute of Public Health Partyzánské náměstí 7 CZ 702 00 Ostrava Czech Republic

Toxicological and Antidoping Center Faculty of Pharmacy Comenius University in Bratislava Odbojárov 10 SK 832 32 Bratislava Slovakia

Zobrazit více v PubMed

Squeglia F., Romano M., Ruggiero A., Berisio R. Molecular players in tuberculosis drug development: Another break in the cell wall. Curr. Med. Chem. 2017;24:3954–3969. doi: 10.2174/0929867324666170208150016. PubMed DOI

Da Silva P.B., Campos D.L., Ribeiro C.M., da Silva I.C., Pavan F.R. New antimycobacterial agents in the pre-clinical phase or beyond: Recent advances in patent literature (2001–2016) Expert Opin. Ther. Pat. 2017;27:269–282. doi: 10.1080/13543776.2017.1253681. PubMed DOI

Wu M.L., Aziz D.B., Dartois V., Dick T. NTM Drug discovery: Status, gaps and the way forward. Drug Discov. Today. 2018;23:1502–1519. doi: 10.1016/j.drudis.2018.04.001. PubMed DOI PMC

Deshpande D., Srivastava S., Chapagain M.L., Lee P.S., Cirrincione K.N., Pasipanodya J.G., Gumbo T. The discovery of ceftazidime/avibactam as an anti-Mycobacterium avium agent. J. Antimicrob. Chemother. 2017;72(Suppl. 2):i36–i42. doi: 10.1093/jac/dkx306. PubMed DOI

Amaral L., Viveiros M., Kristiansen J.E. ‘Non-Antibiotics’: Alternative therapy for the management of MDRTB and MRSA in economically disadvantaged countries. Curr. Drug Targets. 2006;7:887–891. doi: 10.2174/138945006777709539. PubMed DOI

Amaral L., Viveiros M. Thioridazine: A non-antibiotic drug highly effective, in combination with first line anti-tuberculosis drugs, against any form of antibiotic resistance of Mycobacterium tuberculosis due to its multi-mechanisms of action. Antibiotics. 2017;6:3. doi: 10.3390/antibiotics6010003. PubMed DOI PMC

Schmidt R.M., Rosenkranz H.S. Antimicrobial activity of local anesthetics: Lidocaine and procaine. J. Infect. Dis. 1970;121:597–607. doi: 10.1093/infdis/121.6.597. PubMed DOI

Fujii H., Nakajima H., Hirose T., Mochizuki T., Fukaura A., Ota S., Sugihara S., Tazawa H., Takahashi T. Growth inhibition of mycobacteria by lidocaine in fiberoptic bronchoscopic aspirates. JJSRE. 1993;15:108–115. doi: 10.18907/jjsre.15.2_108. DOI

Goldberg L. Pharmacological properties of xylocaine. Sven. Tandl. Tidskr. 1947;40:819–830.

Gordh T. Xylocain—A new local analgesic. Anesthesia. 1949;4:4–9. doi: 10.1111/j.1365-2044.1949.tb05802.x. PubMed DOI

Miescher K. Studies of local anesthetics. Helv. Chim. Acta. 1932;15:163–190. doi: 10.1002/hlca.19320150116. DOI

Agarwal N., Kalra V.K. Studies on the mechanism of action of local anesthetics on proton translocating ATPase from Mycobacterium phlei. Biochim. Biophys. Acta. 1984;764:316–323. doi: 10.1016/0005-2728(84)90102-6. PubMed DOI

Nakayama Y. The electrophoretical analysis of esterase and catalase and its use in taxonomical studies of mycobacteria. Jpn. J. Microbiol. 1967;11:95–101. doi: 10.1111/j.1348-0421.1967.tb00325.x. DOI

Prigozhin D.M., Mavrici D., Huizar J.P., Vansell H.J., Alber T. Structural and biochemical analyses of Mycobacterium tuberculosis N-acetylmuramyl-l-alanine amidase Rv3717 point to a role in peptidoglycan fragment recycling. J. Biol. Chem. 2013;288:31549–31555. doi: 10.1074/jbc.M113.510792. PubMed DOI PMC

Sultana R., Vemula M.H., Banerjee S., Guruprasad L. The PE16 (Rv1430) of Mycobacterium tuberculosis is an esterase belonging to serine hydrolase superfamily of proteins. PLoS ONE. 2013;8:e55320. doi: 10.1371/journal.pone.0055320. PubMed DOI PMC

Vacondio F., Silva C., Mor M., Testa B. Qualitative structure–metabolism relationships in the hydrolysis of carbamates. Drug Metab. Rev. 2010;42:551–589. doi: 10.3109/03602531003745960. PubMed DOI

Moraczewski A.L., Banaszynski L.A., From A.M., White C.E., Smith B.D. Using hydrogen bonding to control carbamate C−N rotamer equilibria. J. Org. Chem. 1998;63:7258–7262. doi: 10.1021/jo980644d. PubMed DOI

Combrink K.D., Denton D.A., Harran S., Ma Z., Chapo K., Yan D., Bonventre E., Roche E.D., Doyle T.B., Robertson G.T., et al. New C25 carbamate rifamycin derivatives are resistant to inactivation by ADP-ribosyl transferases. Bioorg. Med. Chem. Lett. 2007;17:522–526. doi: 10.1016/j.bmcl.2006.10.016. PubMed DOI

Velikorodov A.V., Urlyapova N.G., Daudova A.D. Synthesis and antimycobacterial activity of carbamate derivatives of 1,2-oxazine. Pharm. Chem. J. 2006;40:380–382. doi: 10.1007/s11094-006-0132-5. DOI

Férriz J.M., Vávrová K., Kunc F., Imramovský A., Stolaříková J., Vavříková E., Vinšová J. Salicylanilide carbamates: Antitubercular agents active against multidrug-resistant Mycobacterium tuberculosis strains. Bioorg. Med. Chem. 2010;18:1054–1061. doi: 10.1016/j.bmc.2009.12.055. PubMed DOI

Csöllei J., Búčiová Ľ., Čižmárik J., Kopáčová L. Studies of local anaesthetics CXII. Preparation and activity of dibasic alkylesters of 2-, and 3-alkoxy-substituted phenylcarbamic acids. Českoslov. Farm. 1993;42:127–129. (In Slovak) PubMed

Pavelčík F., Remko M., Čižmárik J., Majer J. Crystal and molecular structure of heptacain hydrochloride. Collect. Czechoslov. Chem. Commun. 1986;51:264–270. doi: 10.1135/cccc19860264. DOI

Waisser K., Doležal R., Palát K., Jr., Čizmárik J., Kaustová J. QSAR Study of antimycobacterial activity of quaternary ammonium salts of piperidinylethyl esters of alkoxysubstituted phenylcarbamic acids. Folia Microbiol. 2006;51:21–24. doi: 10.1007/BF02931444. PubMed DOI

Blaser A., Palmer B.D., Sutherland H.S., Kmentova I., Franzblau S.G., Wan B., Wang Y., Ma Z., Thompson A.M., Denny W.A. Structure−activity relationships for amide-, carbamate-, and urea-linked analogues of the tuberculosis drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824) J. Med. Chem. 2012;55:312–326. doi: 10.1021/jm2012276. PubMed DOI

Gonec T., Pospisilova S., Holanova L., Stranik J., Cernikova A., Pudelkova V., Kos J., Oravec M., Kollar P., Cizek A., et al. Synthesis and antimicrobial evaluation of 1-[(2-substituted phenyl)carbamoyl]naphthalen-2-yl carbamates. Molecules. 2016;21:1189. doi: 10.3390/molecules21091189. PubMed DOI PMC

Malík I., Sedlárová E., Csöllei J., Andriamainty F., Čižmárik J., Kečkéšová S. The physicochemical properties of dibasic alkyl esters of 2- and 3-alkyloxy substituted phenylcarbamic acid. Acta Fac. Pharm. Univ. Comen. 2007;54:136–145.

Čižmárik J., Borovanský A., Švec P. Study of local anesthetics LII. Piperidinoethyl esters of alkoxyphenylcarbamic acids. Acta Fac. Pharm. 1976;29:53–79.

Heywood D.L., Phillips B. The reaction of epichlorohydrin with secondary amines. J. Am. Chem. Soc. 1958;80:1257–1259. doi: 10.1021/ja01538a057. DOI

Schleppnik A.A., Gutsche C.D. Synthesis of polysubstituted triptych-boroxazolidines. J. Org. Chem. 1962;27:3684–3686. doi: 10.1021/jo01057a507. DOI

Dilmohamud B.A., Seeneevassen J., Rughooputh S.D.D.V., Ramasami P. Surface tension and related thermodynamic parameters of alcohols using the Traube stalagmometer. Eur. J. Phys. 2005;26:1079–1084. doi: 10.1088/0143-0807/26/6/015. DOI

Vazquez G., Alvarez E., Navaza J.M. Surface tension of alcohol water + water from 20 to 50 °C. J. Chem. Eng. Data. 1995;40:611–614. doi: 10.1021/je00019a016. DOI

Stopková L., Gališinová J., Šuchtová Z., Čižmárik J., Andriamainty F. Determination of critical micellar concentration of homologous 2-alkoxyphenylcarbamoyloxyethylmorpholinium chlorides. Molecules. 2018;23:1064. doi: 10.3390/molecules23051064. PubMed DOI PMC

Čižmárik J., Borovanský A., Švec P. Study of local anesthetics. LVII. Perhydroazepinylethyl esters of alkoxyphenylcarbamic acids. Česk. Farm. 1976;25:118–121. (In Slovak) PubMed

Blešová M., Čižmárik J., Bachratá M., Bezáková Ž., Borovanský A. Chromatographic parameters, pKa, and surface activity of a series of hydrochlorides of perhydroazepinylethyl esters of alkoxyphenylcarbamic acids and their relation to anaesthetic activity. Collect. Czechoslov. Chem. Commun. 1985;50:1133–1140. doi: 10.1135/cccc19851133. DOI

Yadav L.D.S. Ultraviolet and Visible Spectroscopy. In: Yadav L.D.S., editor. Organic Spectroscopy. Springer; Amsterdam, The Netherlands: 2005. pp. 7–51. DOI

Čižmárik J., Borovanský A. Synthesis, u.v. and i.r. spectra of 2-piperidnoethyl esters of alkyloxyphenylcarbamic acids. Chem. Zvesti. 1975;29:119–123.

Rutkowska E., Pajak K., Jóźwiak K. Lipophilicity–methods of determination and its role in medicinal chemistry. Acta Pol. Pharm. 2013;70:3–18. PubMed

Waisser K., Doležal R., Čižmárik J. Graphic demonstration of the structure–antimycobacterial activity relationships in the series of ester phenylcarbamic acid with piperidine or pyrrolidine moiety. Folia Pharm. Univ. Carol. 2008;37:65–76.

Van de Waterbeemd H., Kansy M., Wagner B., Fischer H. Lipophilicity Measurement by Reversed-Phase High Performance Liquid Chromatography (RP-HPLC) In: Pliška V., Testa B., van de Waterbeemd H., editors. Lipophilicity in Drug Action and Toxicology. Methods and Principles in Medicinal Chemistry. VCh Verlag; Weinheim, Germany: 1996. pp. 73–88.

Valkó K., Slégel P. New chromatographic hydrophobicity index (ϕ0) based on the slope and the intercept of the log k′ versus organic phase concentration plot. J. Chromatogr. A. 1993;631:49–61. doi: 10.1016/0021-9673(93)80506-4. DOI

Du Ch.M., Valko K., Bevan Ch., Reynolds D., Abraham M.H. Rapid method for estimating octanol–water partition coefficient (log Poct) from isocratic RP-HPLC and a hydrogen bond acidity term (A) J. Liq. Chrom. Rel. Technol. 2001;24:635–649. doi: 10.1081/JLC-100103400. DOI

El Tayar N., van de Waterbeemd H., Testa B. Lipophilicity measurements of protonated basic compounds by reversed-phase high-performance liquid chromatography: I. Relationship between capacity factors and the methanol concentration in methanol–water eluents. J. Chromatogr. A. 1985;320:293–304. doi: 10.1016/S0021-9673(01)90507-2. DOI

El Tayar N., van de Waterbeemd H., Testa B. Lipophilicity measurements of protonated basic compounds by reversed-phase high-performance liquid chromatography: II. Procedure for the determination of a lipophilic index measured by reversed-phase high-performance liquid chromatography. J. Chromatogr. A. 1985;320:305–312. doi: 10.1016/S0021-9673(01)90508-4. DOI

Paschke A., Manz M., Schüürmann G. Application of different RP-HPLC methods for the determination of the octanol/water partition coefficient of selected tetrachlorobenzyltoluenes. Chemosphere. 2001;45:721–728. doi: 10.1016/S0045-6535(01)00068-6. PubMed DOI

Montanari M.L.C., Montanari C.A., Piló-Veloso D., Cass Q.B. Estimation of the RP-HPLC lipophilicity parameters log k′, and log kw, a comparison with the hydrophobicity index ϕ0. J. Liq. Chromatogr. Relat. Technol. 1997;20:1703–1715. doi: 10.1080/10826079708006327. DOI

Flieger J., Tatarczak-Michalewska M., Wujec M., Pitucha M., Świeboda R. RP-HPLC Analysis and in vitro identification of antimycobacterial activity of novel thiosemicarbazides and 1,2,4-triazole derivatives. J. Pharm. Biomed. Anal. 2015;107:501–511. doi: 10.1016/j.jpba.2015.01.032. PubMed DOI

Goněc T., Malík I., Csöllei J., Jampílek J., Stolaříková J., Solovič I., Mikuš P., Keltošová S., Kollár P., O’Mahony J., et al. Synthesis and in vitro antimycobacterial activity of novel N-arylpiperazines containing an ethane-1,2-diyl connecting chain. Molecules. 2017;22:2100. doi: 10.3390/molecules22122100. PubMed DOI PMC

Carta A., Paglietti G., Rahbar Nikookar M.E., Sanna P., Sechi L., Zanetti S. Novel substituted quinoxaline 1,4-dioxides with in vitro antimycobacterial and anticandida activity. Eur. J. Med. Chem. 2002;37:355–366. doi: 10.1016/S0223-5234(02)01346-6. PubMed DOI

Moreno E., Gabano E., Torres E., Platts J.A., Ravera M., Aldana I., Monge A., Pérez-Silanes S. Studies on log Po/w of quinoxaline di-N-oxides: A comparison of RP-HPLC experimental and predictive approaches. Molecules. 2011;16:7893–7908. doi: 10.3390/molecules16097893. PubMed DOI PMC

Snyder L.R., Poppe H. Mechanism of solute retention in liquid–solid chromatography and the role of the mobile phase in affecting separation: Competition versus ‘sorption’. J. Chromatogr. A. 1980;184:363–413. doi: 10.1016/S0021-9673(00)93872-X. DOI

Valkó K., Snyder L.R., Glajch J.L. Retention in reversed-phase liquid chromatography as a function of mobile-phase composition. J. Chromatogr. A. 1993;656:501–520. doi: 10.1016/0021-9673(93)80816-Q. DOI

Soczewiński E. Mechanistic molecular model of liquid–solid chromatography: Retention–eluent composition relationships. J. Chromatogr. A. 2002;965:109–116. doi: 10.1016/S0021-9673(01)01278-X. PubMed DOI

Chen N., Yhang Y., Lu P. Effects of molecular structure on the S index in the retention equation in reversed-phase high-performance liquid chromatography. J. Chromatogr. A. 1992;606:35–42. doi: 10.1016/0021-9673(92)85343-R. DOI

Ghose A.K., Crippen G.M. Atomic physicochemical parameters for three-dimensional structure-directed quantitative structure–activity relationships. I. Partition coefficients as a measure of hydrophobicity. J. Comput. Chem. 1986;7:565–577. doi: 10.1002/jcc.540070419. PubMed DOI

Ghose A.K., Crippen G.M. Atomic physicochemical parameters for three-dimensional structure-directed quantitative structure–activity relationships. II. Modeling dispersive and hydrophobic interactions. J. Chem. Inform. Comput. Sci. 1987;27:21–35. doi: 10.1021/ci00053a005. PubMed DOI

Viswanadhan N.V., Ghose K.A., Reyankar R.G., Robins K.R. Atomic physicochemical parameters for three-dimensional structure-directed quantitative structure–activity relationships 4. Additional parameters for hydrophobic and dispersive interactions and their application for an automated superposition of certain naturally occurring nucleoside antibiotics. J. Chem. Inform. Comput. Sci. 1989;29:163–172. doi: 10.1021/ci00063a006. DOI

Broto P., Moreau G., Vandycke C. Molecular structures: Perception, autocorrelation descriptor and SAR studies. System of atomic contributions for the calculation of the n-octanol/water partition coefficients. Eur. J. Med. Chem. 1984;19:71–78.

Leo A. The octanol–water partition coefficient of aromatic solutes: The effect of electronic interactions, alkyl chains, hydrogen bonds, and ortho-substitution. J. Chem. Soc. Perkin Trans. II. 1983;20:825–838. doi: 10.1039/P29830000825. DOI

Tetko I.V., Gasteiger J., Todeschini R., Mauri A., Livingstone D., Ertl P., Palyulin V.A., Radchenko E.V., Zefirov N.S., Makarenko A.S., et al. Virtual computational chemistry laboratory–design and description. J. Comput. Aided Mol. Des. 2005;19:453–463. doi: 10.1007/s10822-005-8694-y. PubMed DOI

Wang R., Gao Y., Lai L. Calculating partition coefficient by atom-additive method. Perspect. Drug Discov. Des. 2000;19:47–66. doi: 10.1023/A:1008763405023. DOI

Cheng T., Zhao Y., Li X., Lin F., Xu Y., Zhang X., Li Y., Wang R., Lai L. Computation of octanol–water partition coefficients by guiding an additive model with knowledge. J. Chem. Inf. Model. 2007;47:2140–2148. doi: 10.1021/ci700257y. PubMed DOI

Moriguchi I., Hirono S., Liu Q., Nakagome I., Matsushita Y. Simple method of calculating octanol/water partition coefficient. Chem. Pharm. Bull. 1992;40:127–130. doi: 10.1248/cpb.40.127. DOI

Sander T., Freyss J., von Korff M., Reich J.R., Rufener C. OSIRIS, an entirely in-house developed drug discovery informatics system. J. Chem. Inf. Model. 2009;49:232–246. doi: 10.1021/ci800305f. PubMed DOI

Molinspiration Cheminformatics, Slovenský Grob, Slovak Republic. [(accessed on 7 June 2018)]; Available online: http://www.molinspiration.com/cgi-bin/properties.

Viswanadhan V.N., Rami Reddy M., Bacquet R.J., Erion M.D. Assessment of methods used for predicting lipophilicity: Application to nucleosides and nucleoside bases. J. Comput. Chem. 1993;14:1019–1026. doi: 10.1002/jcc.540140903. DOI

Tetko I.V., Tanchuk V.Y. Application of associative neural networks for prediction of lipophilicity in ALOGPS 2.1 program. J. Chem. Inf. Comput. Sci. 2002;42:1136–1145. doi: 10.1021/ci025515j. PubMed DOI

Daina A., Michielin O., Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 2017;7:E42717–E42729. doi: 10.1038/srep42717. PubMed DOI PMC

Abdi H., Williams L.J. Principal component analysis. WIREs Comp. Stat. 2010;2:433–459. doi: 10.1002/wics.101. DOI

Carpenter T.S., Kirshner D.A., Lau E.Y., Wong S.E., Nilmeier J.P., Lightstone F.C. A method to predict blood–brain barrier permeability of drug-like compounds using molecular dynamics simulations. Biophys. J. 2014;107:630–641. doi: 10.1016/j.bpj.2014.06.024. PubMed DOI PMC

Norinder U., Haeberlein M. Computational approaches to the prediction of blood–brain distribution. Adv. Drug Deliv. Rev. 2002;54:291–313. doi: 10.1016/S0169-409X(02)00005-4. PubMed DOI

Van de Waterbeemd H., Camenisch G., Folkers G., Chretien J.R., Raevsky O.A. Estimation of blood–brain barrier crossing of drugs using molecular size and shape, and H-bonding descriptors. J. Drug Targets. 1998;6:151–165. doi: 10.3109/10611869808997889. PubMed DOI

Imramovsky A., Pesko M., Kralova K., Vejsova M., Stolarikova J., Vinsova J., Jampilek J. Investigating spectrum of biological activity of 4- and 5-chloro-2-hydroxy-N-[2-(arylamino)-1-alkyl-2-oxoethyl]benz-amides. Molecules. 2011;16:2414–2430. doi: 10.3390/molecules16032414. PubMed DOI PMC

Clinical and Laboratory Standards Institute (CLSI) Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard. 8th ed. CLSI; Wayne, NJ, USA: 2012. pp. 10–56. CLSI Document M11-A8. PubMed

Clinical and Laboratory Standards Institute (CLSI) Performance Standards for Antimicrobial Susceptibility Testing. 24th ed. CLSI; Wayne, NJ, USA: 2014. pp. 106–211. Informational Supplement M100-S24.

Brown-Elliott B.A., Cohen S., Wallace R.J., Jr. Susceptibility Testing of Mycobacteria. In: Schwalbe R., Steele-Moore L., Goodwin A.C., editors. Antimicrobial Susceptibility Testing Protocols. CRC Press (Taylor and Francis Group); Boca Raton, FL, USA: 2007. pp. 243–274.

Waisser K., Dražková K., Čižmárik J., Kaustová J. Antimycobacterial activity of basic ethylesters of alkoxy-substituted phenylcarbamic acids. Folia Microbiol. 2003;48:45–50. doi: 10.1007/BF02931274. PubMed DOI

Jackson D.A. Stopping rules in principal components analysis: A comparison of heuristical and statistical approaches. Ecology. 1993;74:2204–2214. doi: 10.2307/1939574. DOI

Čižmárik J., Waisser K., Doležal R. QSAR Study of antimycobacterial activity of esters of phenylcarbamic acids. Acta Fac. Pharm. Univ. Comen. 2008;55:90–95.

Čižmárik J., Waisser K. Review of potential antituberculotics: Esters of substituted phenylcarbamic acids. Folia Pharm. Univ. Carol. 2008;37:91–94.

Grzegorzewicz A.E., de Sousa-d’Auria C., McNeil M.R., Huc-Claustre E., Jones V., Petit C., Angala S.K., Zemanová J., Wang Q., Belardinelli J.M., et al. Assembling of the Mycobacterium tuberculosis cell wall core. J. Biol. Chem. 2016;291:18867–18879. doi: 10.1074/jbc.M116.739227. PubMed DOI PMC

Kubinyi H. Quantitative structure–activity relationships. 7. The bilinear model, a new model for nonlinear dependence of biological activity on hydrophobic character. J. Med. Chem. 1977;20:625–629. doi: 10.1021/jm00215a002. PubMed DOI

David H.L., Rastogi N., Clavel-Sérès S., Clément F., Thorel M.-F. Structure of the cell envelope of Mycobacterium avium. Zent. Bakteriol. Mikrobiol. Hyg. A. 1987;264:49–66. doi: 10.1016/S0176-6724(87)80124-4. PubMed DOI

Hansch C., Clayton J.M. Lipophilic character and biological activity of drugs II. The parabolic case. J. Pharm. Sci. 1973;62:1–21. doi: 10.1002/jps.2600620102. PubMed DOI

Šula L. WHO Co-operative studies on a simple culture technique for the isolation of mycobacteria. 1. Preparation, lyophilization and reconstitution of a simple semi-synthetic concentrated liquid medium; culture technique; growth pattern of different mycobacteria. Bull. World Health Organ. 1963;29:589–606. PubMed PMC

De Voss J.J., Rutter K., Schroeder B.G., Su H., Zhu Y., Barry C.E., III The salicylate-derived mycobactin siderophores of Mycobacterium tuberculosis are essential for growth in macrophages. Proc. Natl. Acad. Sci. USA. 2000;97:1252–1257. doi: 10.1073/pnas.97.3.1252. PubMed DOI PMC

Schwartz B.D., De Voss J.J. Structure and absolute configuration of mycobactin J. Tetrahedron Lett. 2001;42:3653–3655. doi: 10.1016/S0040-4039(01)00531-7. DOI

Atlas R., Snyder J. Reagents, Stains, and Media: Bacteriology. In: Jorgensen J.H., Pfaller M.A., Carroll K.C., Funke G., Landry M.L., Richter S.S., Warnock D.W., editors. Manual of Clinical Microbiology (2-Volume Set) 11th ed. Volume 1. ASM Press; Washington, DC, USA: 2015. pp. 316–349. DOI

Franzblau S.G., Witzig R.S., McLaughlin J.C., Torres P., Madico G., Hernandez A., Degnan M.T., Cook M.B., Quenzer V.K., Ferguson R.M., et al. Rapid, low-technology MIC determination with clinical Mycobacterium tuberculosis isolates by using the microplate Alamar Blue assay. J. Clin. Microbiol. 1998;36:362–366. PubMed PMC

Long J.E., DeJesus M., Ward D., Baker R.E., Ioerger T., Sassetti C.M. Identifying Essential Genes in Mycobacterium Tuberculosis by Global Phenotypic Profiling. In: Lu L.J., editor. Gene Essentiality. Methods and Protocols. Humana Press (Springer); New York, NY, USA: 2015. pp. 79–98. PubMed DOI

Ringnér M. What is principal component analysis? Nat. Biotechnol. 2008;26:303–304. doi: 10.1038/nbt0308-303. PubMed DOI

Dibasic Derivatives of Phenylcarbamic Acid as Prospective Antibacterial Agents Interacting with Cytoplasmic Membrane

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