1-[2-[({[2-/3-(Alkoxy)phenyl]amino}carbonyl)oxy]-3-(dipropylammonio)propyl]pyrrolidinium/azepan- ium oxalates or dichlorides (alkoxy = butoxy to heptyloxy) were recently described as very promising antimycobacterial agents. These compounds were tested in vitro against Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 (reference and control strains), three methicillin-resistant isolates of S. aureus, and three isolates of vancomycin-resistant E. faecalis. 1-[3-(Dipropylammonio)-2-({[3-(pentyloxy-/hexyloxy-/heptyloxy)phenyl]carbamoyl}oxy)propyl]pyrrolidinium dichlorides showed high activity against staphylococci and enterococci comparable with or higher than that of used controls (clinically used antibiotics and antiseptics). The screening of the cytotoxicity of the compounds as well as the used controls was performed using human monocytic leukemia cells. IC50 values of the most effective compounds ranged from ca. 3.5 to 6.3 µM, thus, it can be stated that the antimicrobial effect is closely connected with their cytotoxicity. The antibacterial activity is based on the surface activity of the compounds that are influenced by the length of their alkoxy side chain, the size of the azacyclic system, and hydro-lipophilic properties, as proven by in vitro experiments and chemometric principal component analyses. Synergistic studies showed the increased activity of oxacillin, gentamicin, and vancomycin, which could be explained by the direct activity of the compounds against the bacterial cell wall. All these compounds demonstrate excellent antibiofilm activity, when they inhibit and disrupt the biofilm of S. aureus in concentrations close to minimum inhibitory concentrations against planktonic cells. Expected interactions of the compounds with the cytoplasmic membrane are proven by in vitro crystal violet uptake assays.

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

Department of Human Pharmacology and Toxicology Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Palackeho 1 61242 Brno Czech Republic

Department of Infectious Diseases and Microbiology Faculty of Veterinary Medicine University of Veterinary and Pharmaceutical Sciences Palackeho 1946 1 612 42 Brno Czech Republic

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

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

Institute of Neuroimmunology Slovak Academy of Sciences Dubravska cesta 9 845 10 Bratislava Slovakia

Regional Centre of Advanced Technologies and Materials Faculty of Science Palacky University Slechtitelu 27 783 71 Olomouc Czech Republic

Zobrazit více v PubMed

Dastidar S.G., Kristiansen J.E., Molnar J., Amaral L. Role of phenothiazines and structurally similar compounds of plant origin in the fight against infections by drug resistant bacteria. Antibiotics. 2013;2:58–72. doi: 10.3390/antibiotics2010058. PubMed DOI PMC

Hamad M., Al-Marzooq F., Orive G., Al-Tel T.H. Superbugs but no drugs: Steps in averting a post-antibiotic era. Drug Discov. Today. 2019;24:2225–2228. doi: 10.1016/j.drudis.2019.08.004. PubMed DOI

Kristiansen J.E., Amaral L. The potential management of resistant infections with non-antibiotics. J. Antimicrob. Chemoth. 1997;40:319–327. doi: 10.1093/jac/40.3.319. PubMed DOI

Amaral L., Lorian V. Effects of chlorpromazine on the cell envelope proteins of Escherichia coli. Antimicrob. Agents Chemother. 1991;35:1923–1924. doi: 10.1128/AAC.35.9.1923. PubMed DOI PMC

Chattopadhyay D., Das S.K., Patra A.R., Bhattacharya S.K. Non-Antibiotics—An alternative for microbial resistance: Scope and hope. In: Ahmad I., Aqil F., editors. New Strategies Combating Bacterial Infection. Wiley-VCH; Weinhiem, Germany: 2009. pp. 89–125.

Schmidt R.M., Rosenkranz H.S. Antimicrobial activity of local anaesthetics: Lidocaine and procaine. J. Infect. Dis. 1970;121:596–607. doi: 10.1093/infdis/121.6.597. PubMed DOI

de Silva S.S., Carvalho J.W.P., Aires C.P., Nitschke M. Disruption of Staphylococcus aureus biofilms using rhamnolipid biosurfactants. J. Dairy Sci. 2017;100:7864–7873. doi: 10.3168/jds.2017-13012. PubMed DOI

Sriram M.I., Kalishwaralal K., Deepak V., Gracerosepat R., Srisakthi K., Gurunathan S. Biofilm inhibition and antimicrobial action of lipopeptide biosurfactant produced by heavy metal tolerant strain Bacillus cereus NK1. Colloids Surf. B. Biointerfaces. 2011;85:174–181. doi: 10.1016/j.colsurfb.2011.02.026. PubMed DOI

Meylheuc T., Van Oss C.J., Bellon-Fontaine M.N. Adsorption of biosurfactant on solid surfaces and consequences regarding the bioadhesion of Listeria monocytogenes LO28. J. Appl. Microbiol. 2001;91:822–832. doi: 10.1046/j.1365-2672.2001.01455.x. PubMed DOI

Wieczorek D., Dobrowolski A., Staszak K., Kwasniewska D., Dubyk P. Surface and antimicrobial activity of sulfobetaines. J. Surfactants Deterg. 2016;19:813–822. doi: 10.1007/s11743-016-1838-3. PubMed DOI PMC

Rewak-Soroczynska J., Paluch E., Siebert A., Szalkiewicz K., Oblak E. Biological activity of glycine and alanine derivatives of quaternary ammonium salts (QASs) against micro-organisms. Lett. Appl. Microbiol. 2019;69:212–220. doi: 10.1111/lam.13195. PubMed DOI

Aydin O.N., Eyigor M., Aydin N. Antimicrobial activity of ropivacaine and other local anaesthetics. Eur. J. Anaesthesiol. 2001;18:687–694. doi: 10.1097/00003643-200110000-00008. PubMed DOI

Mullin G.S., Rubinfeld R.S. The antibacterial activity of topical anesthetics. Cornea. 1997;16:662–665. doi: 10.1097/00003226-199711000-00010. PubMed DOI

Kesici S., Demirci M., Kesici U. Bacterial inhibition efficiency of prilocaine and bupivacaine. Int. Wound J. 2019;16:1185–1189. doi: 10.1111/iwj.13180. PubMed DOI PMC

Pina-Vaz C., Rodrigues A.G., Sansonetty F., Martinez-De-Oliveira J., Fonseca A.F., Mardh P.A. Antifungal activity of local anesthetics against Candida species. Infect. Dis. Obstet. Gynecol. 2000;8:124–137. doi: 10.1155/S1064744900000168. PubMed DOI PMC

Srisatjaluk R.L., Klongnoi B., Wongsirichat N. Antimicrobial effect of topical local anesthetic spray on oral microflora. J. Dent. Anesth. Pain. Med. 2016;16:17–24. doi: 10.17245/jdapm.2016.16.1.17. PubMed DOI PMC

Johnson S.M., Saint J., Barbara E., Dine A.P. Local anesthetics as antimicrobial agents: A review. Surg. Infect. 2008;9:205–213. doi: 10.1089/sur.2007.036. PubMed DOI

Mutlu E. In vitro investigation of the antibacterial effects of lidocaine and bupivacaine alone and in combinations with fentanyl. Turk. Klin. J. Med. Sci. 2018;38:334–339. doi: 10.5336/medsci.2018-61628. DOI

Kramer A., Sorgatz K., Hoppe H., Meyer F.U. Bacteriostatic and antiseptic efficacy of selected anaesthetics individually and in combination with an antiseptic mouthwash. Hygiene Medizin. 1994;19:527–534.

Razavi B.M., Fazly-Bazzaz B.S. A review and new insights to antimicrobial action of local anesthetics. Eur. J. Clin. Microbiol. Infect. Dis. 2019;38:991–1002. doi: 10.1007/s10096-018-03460-4. PubMed DOI

Abdelli F., Jardak M., Elloumi J., Stien D., Cherif S., Mnif S., Aifa S. Antibacterial, anti-adherent and cytotoxic activities of surfactin (s) from a lipolytic strain Bacillus safensis F4. Biodegradation. 2019;30:287–300. doi: 10.1007/s10532-018-09865-4. PubMed DOI

Lewis K. Riddle of biofilm resistance. Antimicrob. Agents Chemother. 2001;45:999–1007. doi: 10.1128/AAC.45.4.999-1007.2001. PubMed DOI PMC

Jamal M., Ahmad W., Andleeb S., Jalil F., Imran M., Nawaz M.A., Kamil M.A. Bacterial biofilm and associated infections. J. Chin. Med. Assoc. 2018;81:7–11. doi: 10.1016/j.jcma.2017.07.012. PubMed DOI

Scott VanEpps J., Younger J.G. Implantable device related infection. Shock. 2016;46:597–608. doi: 10.1097/SHK.0000000000000692. PubMed DOI PMC

Azevedo M.M., Cobrado L., Silva-Dias A., Pina-Vaz C., Rodrigues A.G. Prevention and eradication of biofilm in medical indwelling devices. In: Atta-ur-Rahman, editor. Frontiers in Clinical Drug Research—Anti Infectives. Bentham Science Publishers; Sharjah, UAE: 2017. pp. 204–232.

Khatoon Z., McTiernan C.D., Suuronen E.J., Mah T.F., Alarcona E.I. Bacterial biofilm formation on implantable devices and approaches to its treatment and prevention. Heliyon. 2018;4:e01067. doi: 10.1016/j.heliyon.2018.e01067. PubMed DOI PMC

Mandakhalikar K.D., Chua R.R., Tambyah P.A. New technologies for prevention of catheter associated urinary tract infection. Curr. Treat. Options Infect. Dis. 2016;8:24–41. doi: 10.1007/s40506-016-0069-5. DOI

Gominet M., Compain F., Beloin C., Lebeaux D. Central venous catheters and biofilms: Where do we stand in 2017? APMIS. 2017;125:365–375. doi: 10.1111/apm.12665. PubMed DOI

Menezes F.G., Correa L., Medina-Pestana J.O., Aguiar W.F., Camargo L.F.A. A randomized clinical trial comparing Nitrofurazone-coated and uncoated urinary catheters in kidney transplant recipients: Results from a pilot study. Transpl. Infect. Dis. 2019;21:e13031. doi: 10.1111/tid.13031. PubMed DOI

Doherty W. Instillagel: An anaesthetic antiseptic gel for use in catheterization. Br. J. Nurs. 1999;8:109–112. doi: 10.12968/bjon.1999.8.2.6709. PubMed DOI

Wilson M.C.R. Biofilm and other causes of pain in catheterization. Br. J. Community Nurs. 2009;14:102–113. doi: 10.12968/bjcn.2009.14.3.40090. PubMed DOI

Lai N.M., Chaiyakunapruk N., Lai N.A., O’Riordan E., Pau W.S.C., Saint S. Catheter impregnation, coating or bonding for reducing central venous catheter-related infections in adults. Cochrane Database Syst. Rev. 2016;3:CD007878. doi: 10.1002/14651858.CD007878.pub3. PubMed DOI PMC

Chong H.Y., Lai N.M., Apisarnthanarak A., Chaiyakunapruk N. Comparative efficacy of antimicrobial central venous catheters in reducing catheter-related bloodstream infections in adults: Abridged cochrane systematic review and network meta-analysis. Clin. Infect. Dis. 2017;64:S131–S140. doi: 10.1093/cid/cix019. PubMed DOI

Wang H., Tong H., Liu H., Wang Y., Wang R., Gao H., Yu P., Lv Y., Chen S., Wang G., et al. Effectiveness of antimicrobial-coated central venous catheters for preventing catheter-related blood-stream infections with the implementation of bundles: A systematic review and network meta-analysis. Ann. Intensive Care. 2018;8:71. doi: 10.1186/s13613-018-0416-4. PubMed DOI PMC

Dang F.P., Li H.J., Tian J.H. Comparative efficacy of 13 antimicrobial dressings and different securement devices in reducing catheter-related bloodstream infections: A Bayesian network meta-analysis. Medicine. 2019;98:e14940. doi: 10.1097/MD.0000000000014940. PubMed DOI PMC

Yeung S.S.T., Loshak H. Coated and Uncoated Central Venous Catheters: A Review of Comparative Clinical Effectiveness and Safety. Canadian Agency for Drugs and Technologies in Health; Ottawa, ON, Canada: Jan, 2019. CADTH Rapid Response Report: Summary with Critical Appraisal. PubMed

Majeed A., Sagar F., Latif A., Hassan H., Iftikhar A., Darouiche R.O., Mohajer M.A. Does antimicrobial coating and impregnation of urinary catheters prevent catheter-associated urinary tract infection? A review of clinical and preclinical studies. Expert Rev. Med. Devices. 2019;16:809–820. doi: 10.1080/17434440.2019.1661774. PubMed DOI

Al-Qahtani M., Safan A., Jassim G., Abadla S. Efficacy of anti-microbial catheters in preventing catheter associated urinary tract infections in hospitalized patients: A review on recent updates. J. Infect. Public Health. 2019;12:760–766. doi: 10.1016/j.jiph.2019.09.009. PubMed DOI

Monteiro C., Costa F., Pirttila A.M., Tejesvi M.V., Cristina M., Martins L. Prevention of urinary catheter-associated infections by coating antimicrobial peptides from crowberry endophytes. Sci. Rep. 2019;9:10753. doi: 10.1038/s41598-019-47108-5. PubMed DOI PMC

Andersen M.J., Flores-Mireles A.L. Urinary catheter coating modifications: The race against catheter-associated infections. Coatings. 2020;10:23. doi: 10.3390/coatings10010023. DOI

Otto M. Staphylococcal biofilms. Curr. Top. Microbiol. Immunol. 2008;322:207–228. PubMed PMC

Malheiro J., Simoes M. Antimicrobial resistance of biofilms in medical devices. In: Deng Y., Lv W., editors. Biofilms and Implantable Medical Devices. Woodhead Publishing & Elsevier; Duxford, UK: 2017. pp. 97–113.

Larsen T., Fiehn N.E. Resistance of Streptococcus sanguis biofilms to antimicrobial agents. APMIS. 1996;104:280–284. doi: 10.1111/j.1699-0463.1996.tb00718.x. PubMed DOI

Olsen I. Biofilm-specific antibiotic tolerance and resistance. Eur. J. Clin. Microbiol. Infect. Dis. 2015;34:877–886. doi: 10.1007/s10096-015-2323-z. PubMed DOI

Pace J.L., Rupp M.E., Finch R.G. Biofilms, Infection, and Antimicrobial Therapy. 1st ed. CRC Press, Taylor & Francis Group; Boca Raton, FL, USA: 2006.

Vetas D., Dimitropoulou E., Mitropoulou G., Kourkoutas Y., Giaouris E. Disinfection efficiencies of sage and spearmint essential oils against planktonic and biofilm Staphylococcus aureus cells in comparison with sodium hypochlorite. Int. J. Food Microbiol. 2017;257:19–25. doi: 10.1016/j.ijfoodmicro.2017.06.003. PubMed DOI

Kwiecinska-Pirog J., Bogiel T., Gospodarek E. Effects of ceftazidime and ciprofloxacin on biofilm formation in Proteus mirabilis rods. J. Antibiot. 2013;66:593–597. doi: 10.1038/ja.2013.59. PubMed DOI

Jampilek J. Design and discovery of new antibacterial agents: Advances, perspectives, challenges. Curr. Med. Chem. 2018;25:4972–5006. doi: 10.2174/0929867324666170918122633. PubMed DOI

Singha P., Locklin J., Handa H. A review of the recent advances in antimicrobial coatings for urinary catheters. Acta Biomater. 2017;50:20–40. doi: 10.1016/j.actbio.2016.11.070. PubMed DOI PMC

Walters M.C., Roe F., Bugnicourt A., Franklin M.J., Stewart P.S. Contributions of antibiotic penetration, oxygen limitation, and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin. Antimicrob. Agents Chemother. 2003;47:317–323. doi: 10.1128/AAC.47.1.317-323.2003. PubMed DOI PMC

Hall C.W., Mah T.F. Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria. FEMS Microbiol. Rev. 2017;41:276–301. doi: 10.1093/femsre/fux010. PubMed DOI

Borrielo G., Richards L., Ehrlich G.D., Stewart P.S. Arginine or nitrate enhances antibiotic susceptibility of Pseudomonas aeruginosa in biofilms. Antimicrob. Agents Chemother. 2006;50:382–384. doi: 10.1128/AAC.50.1.382-384.2006. PubMed DOI PMC

Van Ecker H., Sass A., Bazzini S., De Roy K., Udine C., Messiaen T., Coenye T. Biofilm-grown Burkholderia cepacia complex cells survive antibiotic treatment by avoiding production of reactive oxygen species. PLoS ONE. 2013;8:58943. doi: 10.1371/journal.pone.0058943. PubMed DOI PMC

Malik I., Csollei J., Solovic I., Pospisilova S., Michnova H., Jampilek J., Cizek A., Kapustikova I., Curillova J., Pechacova M., et al. Dibasic derivatives of phenylcarbamic acid against mycobacterial strains: Old drugs and new tricks? Molecules. 2018;23:2493. doi: 10.3390/molecules23102493. PubMed DOI PMC

Csollei J., Buciova L., Cizmarik J., Kopacova L. Studies of local anaesthetics CXII. Preparation and activity of dibasic alkylesters of 2-, and 3-alkoxy-substituted phenylcarbamic acids. Ceskoslov. Farm. 1993;42:127–129. PubMed

Oravcova V., Zurek L., Townsend A., Clark A.B., Ellis J.C., Cizek A. American crows as carriers of vancomycin-resistant enterococci with vanA gene. Environ. Microbiol. 2014;16:939–949. doi: 10.1111/1462-2920.12213. PubMed DOI

Zadrazilova I., Pospisilova S., Masarikova M., Imramovsky A., Monreal-Ferriz J., Vinsova J., Cizek A., Jampilek J. Salicylanilide carbamates: Promising antibacterial agents with high in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) Eur. J. Pharm. Sci. 2015;77:197–207. doi: 10.1016/j.ejps.2015.06.009. PubMed DOI

Tengler J., Kapustikova I., Pesko M., Govender R., Keltosova S., Mokry P., Kollar P., O´Mahony J., Coffey A., Kralova K., et al. Synthesis and biological evaluation of 2-hydroxy-3-[(2-aryloxyethyl)amino]propyl 4-[(alkoxycarbonyl)amino]benzoates. Sci. World J. 2013;2013:274570. doi: 10.1155/2013/274570. PubMed DOI PMC

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]- benzamides. Molecules. 2011;16:2414–2430. doi: 10.3390/molecules16032414. PubMed DOI PMC

Pauk K., Zadrazilova I., Imramovsky A., Vinsova J., Pokorna M., Masarikova M., Cizek A., Jampilek J. New derivatives of salicylamides: Preparation and antimicrobial activity against various bacterial species. Bioorg. Med. Chem. 2013;21:6574–6581. doi: 10.1016/j.bmc.2013.08.029. PubMed DOI

Pere P., Lindgren L., Vaara M. Poor antibacterial effect of ropivacaine: Comparison with bupivacaine. Anesthesiology. 1999;91:884–886. doi: 10.1097/00000542-199909000-00047. PubMed DOI

ROCHE . Roche Diagnostics GmbH; Mannheim, Germany: 2011. [(accessed on 24 January 2020)]. Cell Proliferation Reagent WST-1. Available online: https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Roche/Bulletin/1/cellprorobul.pdf.

Kos J., Nevin E., Soral M., Kushkevych I., Gonec T., Bobal P., Kollar P., Coffey A., O´Mahony J., Liptaj T., et al. Synthesis and antimycobacterial properties of ring-substituted 6-hydroxynaphthalene- 2-carboxanilides. Bioorg. Med. Chem. 2015;23:2035–2043. doi: 10.1016/j.bmc.2015.03.018. PubMed DOI

Lim E.J., Yoon Y.J., Heo J., Lee T.H., Kim Y.H. Ciprofloxacin enhances TRAIL-induced apoptosis in lung cancer cells by upregulating the expression and protein stability of death receptors through CHOP expression. Int. J. Mol. Sci. 2018;19:3187. doi: 10.3390/ijms19103187. PubMed DOI PMC

Suffness M., Douros J. Current status of the NCI plant and animal product program. J. Nat. Prod. 1982;45:1–14. doi: 10.1021/np50019a001. PubMed DOI

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

van den Berg R.A., Hoefsloot H.C., Westerhuis J.A., Smilde A.K., van der Werf M.J. Centering, scaling, and transformations: Improving the biological information content of metabolomics data. BMC Genom. 2006;7:142–156. doi: 10.1186/1471-2164-7-142. PubMed DOI PMC

Bro R., Smilde A.K. Principal component analysis. Anal. Methods. 2014;6:2812–2831. doi: 10.1039/C3AY41907J. DOI

Eriksson L., Jaworska J., Worth A.P., Cronin M.T., McDowell R.M., Gramatica P. Methods for reliability and uncertainty assessment and for applicability evaluations of classification- and regression-based QSARs. Environ. Health Perspect. 2003;111:1361–1375. doi: 10.1289/ehp.5758. PubMed DOI PMC

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

Hauke J., Kossowski T. Comparison of values of Pearson’s and Spearman’s correlation coefficients on the same sets of data. Quaest. Geograph. 2011;30:87–93. doi: 10.2478/v10117-011-0021-1. DOI

Schwalbe R., Steele-Moore L., Goodwin A.C. Antimicrobial Susceptibility Testing Protocols. 1st ed. CRC Press; Boca Raton, FL, USA: 2007.

Bonapace C.R., Bosso J.A., Friedrich L.V., White R.L. Comparison of methods of interpretation of checkerboard synergy testing. Diagn. Microbiol. Infect. Dis. 2002;44:363–366. doi: 10.1016/S0732-8893(02)00473-X. PubMed DOI

Breukink E., De Kruijff B. Lipid II as a target for antibiotics. Nat. Rev. Drug Discov. 2006;5:321–323. doi: 10.1038/nrd2004. PubMed DOI

Tipper D.J., Strominger J.L. Mechanism of action of penicillins: A proposal based on their structural similarity to acyl-D-alanyl-D-alanine. Proc. Natl. Acad. Sci. USA. 1965;54:1133–1141. doi: 10.1073/pnas.54.4.1133. PubMed DOI PMC

Arias C.A., Murray B.E. The rise of the Enterococcus: Beyond vancomycin resistance. Nat. Rev. Microbiol. 2012;10:266–278. doi: 10.1038/nrmicro2761. PubMed DOI PMC

Stapleton P.D., Taylor P.W. Methicillin resistance in Staphylococcus aureus: Mechanisms and modulation. Sci. Prog. 2002;85:57–72. doi: 10.3184/003685002783238870. PubMed DOI PMC

Cetinkaya Y., Falk P., Mayhall C.G. Vancomycin-resistant enterococci. Clin. Microbiol. Rev. 2000;13:686–707. doi: 10.1128/CMR.13.4.686. PubMed DOI PMC

Cha J.O., Park Y.K., Lee Y.S., Chung G.T. In vitro biofilm formation and bactericidal activities of methicillin-resistant Staphylococcus aureus clones prevalent in Korea. Diagn. Microbiol. Infect. Dis. 2011;70:112–118. doi: 10.1016/j.diagmicrobio.2010.11.018. PubMed DOI

Devi K.P., Nisha S.A., Sakthivel R., Pandian S.K. Eugenol (an essential oil of clove) acts as an antibacterial agent against Salmonella typhi by disrupting the cellular membrane. J. Ethnopharmacol. 2010;130:107–115. doi: 10.1016/j.jep.2010.04.025. PubMed DOI

Pospisilova S., Kos J., Michnova H., Kapustikova I., Strharsky T., Oravec M., Moricz A.M., Bakonyi J., Kauerova T., Kollar P., et al. Synthesis and spectrum of biological activities of novel N-arylcinnamamides. Int. J. Mol. Sci. 2018;19:2318. doi: 10.3390/ijms19082318. PubMed DOI PMC

Clinical and Laboratory Standards Institute . Performance Standards for Antimicrobial Susceptibility Testing. CLSI; Wayne, PA, USA: 2012. The 8th Informational Supplement Document. M100-S22.

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

New Unnatural Gallotannins: A Way toward Green Antioxidants, Antimicrobials and Antibiofilm Agents