Insight into antistaphylococcal effect of chlorinated 1-hydroxy-naphthalene-2-carboxanilides: Original scientific article

Lucia Vrablova; Tomas Gonec; Petra Majerova; Andrej Kovac; Dominika Kos; Peter Kollar; Jiri Kos; Alois Cizek; Tereza Kauerova; Josef Jampilek

doi:10.5599/admet.2684

Authors

Lucia Vrablova Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 842 15 Bratislava, Slovakia https://orcid.org/0009-0008-4701-5265
Tomas Gonec Department of Chemical Drugs, Faculty of Pharmacy, Masaryk University, Palackeho tr. 1946/1, 612 00 Brno, Czech Republic https://orcid.org/0000-0003-3712-8641
Petra Majerova Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, 845 10 Bratislava, Slovakia https://orcid.org/0000-0001-9239-6425
Andrej Kovac Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, 845 10 Bratislava, Slovakia https://orcid.org/0000-0002-3223-8705
Dominika Kos Department of Molecular Pharmacy, Faculty of Pharmacy, Masaryk University, Palackeho tr. 1946/1, 612 00 Brno, Czech Republic https://orcid.org/0000-0001-7994-313X
Peter Kollar Department of Pharmacology and Toxicology, Faculty of Pharmacy, Masaryk University, Palackeho tr. 1946/1, 612 00 Brno, Czech Republic https://orcid.org/0000-0003-2265-1528
Jiri Kos Department of Biochemistry, Faculty of Medicine, Masaryk University, Kamenice 5, Brno 625 00, Czech Republic https://orcid.org/0000-0002-3589-4361
Alois Cizek Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Palackeho tr. 1946/1, 612 42 Brno, Czech Republic https://orcid.org/0000-0001-5706-4601
Tereza Kauerova Department of Pharmacology and Toxicology, Faculty of Pharmacy, Masaryk University, Palackeho tr. 1946/1, 612 00 Brno, Czech Republic https://orcid.org/0000-0003-2854-511X
Josef Jampilek Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 842 15 Bratislava, Slovakia https://orcid.org/0000-0003-2003-9052

DOI:

https://doi.org/10.5599/admet.2684

Keywords:

Lipophilicity, antistaphylococcal activity, cytotoxicity, MTT assay, chemoproteomic analysis

Abstract

Background and purpose: New compounds and innovative therapeutic approaches are trying to prevent antimicrobial resistance, which has become a global health challenge. Experimental approach: This study includes a series of twelve mono-, di- and trichlorinated 1-hydroxynaphthalene-2-carboxanilides designed as multitarget agents. All compounds were evaluated for their antistaphylococcal activity. Furthermore, MTT assay and chemoproteomic analysis of selected compounds were performed. Cytotoxicity in human cells was also tested. Key results: N-(3,5-Dichlorophenyl)-1-hydroxynaphthalene-2-carboxamide (10) demon-strated activity comparable to or higher than clinically used drugs, with minimum inhibitory concentrations (MICs) of 0.37 μM. The compound was equally effective against clinical isolates of methicillin-resistant S. aureus. On the other hand, compound 10 showed 96 % inhibition of S. aureus respiration only at a concentration of 16× MIC. Chemoproteomic analysis revealed that the effect of agent 10 on staphylococci resulted in the downregulation of four proteins. This compound expressed no in vitro cytotoxicity up to a concentration of 30 μM. Conclusion: From the set of tested mono-, di- and trisubstituted derivatives, it is evident that the position of chlorine atoms is decisive for significant antistaphylococcal activity. Inhibition of energy metabolism does not appear to be one of the main mechanisms of action of compound 10; on the contrary, the antibacterial effect may likely be contributed by downregulation of proteins (especially ATP-dependent protease ATPase subunit HslU) involved in processes essential for bacterial survival and growth, such as protein, nucleotide/nucleic acid synthesis and efficient protein repair/degradation.

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References

WHO Bacterial Priority Pathogens List, 2024. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance (accessed on 10 February 2025).

WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report: 2022. https://www.who.int/publications/i/item/9789240062702 (accessed on 10 February 2025).

Assessing the health burden of infections with antibiotic-resistant bacteria in the EU/EEA, 2016-2020. European Centre for Disease Prevention and Control (ECDC): Stockholm, Sweden, 2022. https://www.ecdc.europa.eu/en/publications-data/health-burden-infections-antibiotic-resistant-bacteria-2016-2020 (accessed on 10 February 2025).

H. Fongang, A.T. Mbaveng, V. Kuete. Global burden of bacterial infections and drug resistance. in Advances in Botanical Research, V. Kuete (Ed.), Academic Press & Elsevier, Amsterdam, Netherlands, 2023, pp.1-20. https://doi.org/10.1016/bs.abr.2022.08.001 DOI: https://doi.org/10.1016/bs.abr.2023.12.013

National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Long-Term Health and Economic Effects of Antimicrobial Resistance in the United States. in Combating Antimicrobial Resistance and Protecting the Miracle of Modern Medicine, G.H. Palmer, G.J. Buckley (Eds.), National Academies Press, Washington D.C., USA, 2022. https://nap.nationalacademies.org/catalog/26350/combating-antimicrobial-resistance-and-protecting-the-miracle-of-modern-medicine (accessed on 10 February 2025).

GBD 2021 Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance 1990-2021: A systematic analysis with forecasts to 2050. Lancet 404 (2024) 1199-1226. https://doi.org/10.1016/s0140-6736(24)01867-1 DOI: https://doi.org/10.1016/S0140-6736(24)01867-1

GBD 2019 Antimicrobial Resistance Collaborators. Global mortality associated with 33 bacterial pathogens in 2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet 400 (2022) 2221-2248. https://doi.org/10.1016/S0140-6736(22)02185-7 DOI: https://doi.org/10.1016/S0140-6736(22)02185-7

J. Jampilek. Design and discovery of new antibacterial agents: Advances, perspectives, challenges. Current Medicinal Chemistry 25 (2018) 4972-5006. https://doi.org/10.2174/0929867324666170918122633 DOI: https://doi.org/10.2174/0929867324666170918122633

M. Miethke, M. Pieroni, T. Weber, M. Brönstrup, P. Hammann, L. Halby, P.B. Arimondo, P. Glaser, B. Aigle, H.B. Bode, R. Moreira, Y. Li, A. Luzhetskyy, M.H. Medema, J.L. Pernodet, M. Stadler, J.R. Tormo, O. Genilloud, A.W. Truman, K.J. Weissman, E. Takano, S. Sabatini, E. Stegmann, H. Brötz-Oesterhelt, W. Wohlleben, M. Seemann, M. Empting, A.K.H. Hirsch, B. Loretz, C.M. Lehr, A. Titz, J. Herrmann, T. Jaeger, S. Alt, T. Hesterkamp, M. Winterhalter, A. Schiefer, K. Pfarr, A. Hoerauf, H. Graz, M. Graz, M. Lindvall, S. Ramurthy, A. Karlén, M. van Dongen, H. Petkovic, A. Keller, F. Peyrane, S. Donadio, L. Fraisse, L.J.V. Piddock, I.H. Gilbert, H.E. Moser, R. Müller. Towards the sustainable discovery and development of new antibiotics. Nature Reviews Chemistry 5 (2021) 726-749. https://doi.org/10.1038/s41570-021-00313-1 DOI: https://doi.org/10.1038/s41570-021-00313-1

N.J. Ayon. High-throughput screening of natural product and synthetic molecule libraries for antibacterial drug discovery. Metabolites 13 (2023) 625. https://doi.org/10.3390/metabo13050625 DOI: https://doi.org/10.3390/metabo13050625

N.K. Boyd, C. Teng, C.R. Frei. Brief overview of approaches and challenges in new antibiotic development: A focus on drug repurposing. Frontiers in Cellular and Infection Microbiology 11 (2021) 684515. https://doi.org/10.3389/fcimb.2021.684515 DOI: https://doi.org/10.3389/fcimb.2021.684515

S.K. Mondal, S. Chakraborty, S. Manna, S.M. Mandal. Antimicrobial nanoparticles: Current landscape and future challenges. RSC Pharmaceutics 1 (2024) 388-402. https://doi.org/10.1039/D4PM00032C DOI: https://doi.org/10.1039/D4PM00032C

D.A. Gray, M. Wenzel. Multitarget approaches against multiresistant superbugs. ACS Infectious Diseases 6 (2020) 1346-1365. https://doi.org/10.1021/acsinfecdis.0c00001 DOI: https://doi.org/10.1021/acsinfecdis.0c00001

C.J. Suckling, I.S. Hunter, F.J. Scott. Multitargeted anti-infective drugs: Resilience to resistance in the antimicrobial resistance era. Future Drug Discovery 4 (2022) FDD73. https://doi.org/10.4155/fdd-2022-0001 DOI: https://doi.org/10.4155/fdd-2022-0001

J. Feng, Y. Zheng, W. Ma, A. Ihsan, H. Hao, G. Cheng, X. Wang. Multitarget antibacterial drugs: An effective strategy to combat bacterial resistance. Pharmacology & Therapeutics 252 (2023) 108550. https://doi.org/10.1016/j.pharmthera.2023.108550 DOI: https://doi.org/10.1016/j.pharmthera.2023.108550

J.B. Bremner. An update review of approaches to multiple action-based antibacterials. Antibiotics 12 (2023) 865. https://doi.org/10.3390/antibiotics12050865 DOI: https://doi.org/10.3390/antibiotics12050865

G. Stelitano, J.C. Sammartino, L.R. Chiarelli. Multitargeting compounds: A promising strategy to overcome multi-drug resistant tuberculosis. Molecules 25 (2020) 1239. https://doi.org/10.3390/molecules25051239 DOI: https://doi.org/10.3390/molecules25051239

M. Lagadinou, M.O. Onisor, A. Rigas, D.V. Musetescu, D. Gkentzi, S.F. Assimakopoulos, G. Panos, M. Marangos. Antimicrobial properties on non-antibiotic drugs in the era of increased bacterial resistance. Antibiotics 9 (2020) 107. https://doi.org/10.3390/antibiotics9030107 DOI: https://doi.org/10.3390/antibiotics9030107

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

I. Kushkevych, P. Kollar, A.L. Ferreira, D. Palma, A. Duarte, M.M. Lopes, M. Bartos, K. Pauk, A. Imram¬ovsky, J. Jampilek. Antimicrobial effect of salicylamide derivatives against intestinal sulfate-reducing bacteria. Journal of Applied Biomedicine 14 (2016) 125-130. https://doi.org/10.1016/j.jab.2016.01.005 DOI: https://doi.org/10.1016/j.jab.2016.01.005

L. Borbala-Horvath, M. Kratky, V. Pflegr, E. Mahes, G. Gyulai, G. Kohut, A. Babiczky, B. Biri-Kovacs, Z. Baranyai, J. Vinsova, S Bosze. Host cell targeting of novel antimycobacterial 4-aminosalicylic acid derivatives with tuftsin carrier peptides. European Journal of Pharmaceutics and Biopharmaceutics 174 (2022) 111-130. https://doi.org/10.1016/j.ejpb.2022.03.009 DOI: https://doi.org/10.1016/j.ejpb.2022.03.009

G. Paraskevopoulos, S. Monteiro, R. Vosatka, M. Kratky, L. Navratilova, F. Trejtnar, J. Stolarikova, J. Vinsova. Novel salicylanilides from 4,5-dihalogenated salicylic acids: Synthesis, antimicrobial activity and cytotoxicity. Bioorganic and Medicinal Chemistry 25 (2017) 1524-1532. https://doi.org/10.1016/j.bmc.2017.01.016 DOI: https://doi.org/10.1016/j.bmc.2017.01.016

M. Alhashimi, A. Mayhoub, M.N. Seleem. Repurposing salicylamide for combating multidrug-resistant Neisseria gonorrhoeae. Antimicrobial Agents and Chemotherapy 63 (2019) e01225-19. https://doi.org/10.1128/aac.01225-19 DOI: https://doi.org/10.1128/AAC.01225-19

H. Almolhim, A.E.M. Elhassanny, N.S. Abutaleb, A.S. Abdelsattar, M.N. Seleem, P.R. Carlier. Substituted salicylic acid analogs offer improved potency against multidrug-resistant Neisseria gonorrhoeae and good selectivity against commensal vaginal bacteria. Scientific Reports 13 (2023) 14468. https://doi.org/10.1038/s41598-023-41442-5 DOI: https://doi.org/10.1038/s41598-023-41442-5

T. Yokoyama, M. Mizuguchi, Y. Nabeshima, Y. Nakagawa, T. Okada, N. Toyooka, K. Kusaka. Rafoxanide, a salicylanilide anthelmintic, interacts with human plasma protein transthyretin. The FEBS Journal 290 (2023) 5158-5170. https://doi.org/10.1111/febs.16915 DOI: https://doi.org/10.1111/febs.16915

T. Kauerova, M.J. Perez-Perez, P. Kollar. Salicylanilides and their anti-cancer properties. International Journal of Molecular Sciences 24 (2023) 1728. https://doi.org/10.3390/ijms24021728 DOI: https://doi.org/10.3390/ijms24021728

J. Otevrel, Z. Mandelova, M. Pesko, J. Guo, K. Kralova, F. Sersen, M. Vejsova, D.S. Kalinowski, Z. Kovacevic, A. Coffey, J. Csollei, D.R. Richardson, J. Jampilek. Investigating the spectrum of biological activity of ring-substituted salicylanilides and carbamoylphenylcarbamates. Molecules 15 (2010) 8122-8142. https://doi.org/10.3390/molecules15118122 DOI: https://doi.org/10.3390/molecules15118122

A. Imramovsky, M. Pesko, J.M. Ferriz, K. Kralova, J. Vinsova, J Jampilek. Photosynthesis-Inhibiting efficiency of 4-chloro-2-(chlorophenylcarbamoyl)phenyl alkylcarbamates. Bioorganic & Medicinal Chemistry Letters 21 (2011) 4564-4567. https://doi.org/10.1016/j.bmcl.2011.05.118 DOI: https://doi.org/10.1016/j.bmcl.2011.05.118

T. Gonec, J. Kos, I. Zadrazilova, M. Pesko, S. Keltosova, J. Tengler, P. Bobal, P. Kollar, A. Cizek, K. Kralova, J. Jampilek. Antimycobacterial and herbicidal activity of ring-substituted 1-hydroxynaphthalene-2-carboxanilides. Bioorganic and Medicinal Chemistry 21 (2013) 6531-6541. https://doi.org/10.1016/j.bmc.2013.08.030 DOI: https://doi.org/10.1016/j.bmc.2013.08.030

T. Gonec, S. Pospisilova, T. Kauerova, J. Kos, J. Dohanosova, M. Oravec, P. Kollar, A. Coffey, T. Liptaj, A. Cizek, J. Jampilek. N-Alkoxyphenylhydroxynaphthalenecarboxamides and their antimycobacterial activity. Molecules 21 (2016) 1068. https://doi.org/10.3390/molecules21081068 DOI: https://doi.org/10.3390/molecules21081068

H. Michnova, S. Pospisilova, T. Gonec, I. Kapustikova, P. Kollar, V. Kozik, R. Musiol, I. Jendrzejewska, J. Vanco, Z. Travnicek, A. Cizek, A. Bak, J. Jampilek. Bioactivity of methoxylated and methylated 1-hydroxynaphthalene-2-carboxanilides: comparative molecular surface analysis. Molecules 24 (2019) 2991. https://doi.org/10.3390/molecules24162991 DOI: https://doi.org/10.3390/molecules24162991

E. Spaczynska, A. Mrozek-Wilczkiewicz, K. Malarz, J. Kos, T. Gonec, M. Oravec, R. Gawecki, A. Bak, J. Dohanosova, I. Kapustikova, T. Liptaj, J. Jampilek, R. Musiol. Design and synthesis of anti-cancer 1-hydroxynaphthalene-2-carboxanilides with a p53 independent mechanism of action. Scientific Reports 9 (2019) 6387. https://doi.org/10.1038/s41598-019-42595-y DOI: https://doi.org/10.1038/s41598-019-42595-y

T. Kauerova, T. Gonec, J. Jampilek, S. Hafner, A.K. Gaiser, T. Syrovets, R. Fedr, K. Soucek, P. Kollar. Ring-substituted 1-hydroxynaphthalene-2-carboxanilides inhibit proliferation and trigger mitochondria-mediated apoptosis. International Journal of Molecular Sciences 21 (2020) 3416. https://doi.org/10.3390/ijms21103416 DOI: https://doi.org/10.3390/ijms21103416

H. Terada, S. Goto, K. Yamamoto, I. Takeuchi, Y. Hamada, K. Miyake. Structural requirements of salicylanilides for uncoupling activity in mitochondria: quantitative analysis of structure-uncoupling relationships. Biochimica et Biophysica Acta 936 (1988) 504-512. https://doi.org/10.1016/0005-2728(88)90027-8 DOI: https://doi.org/10.1016/0005-2728(88)90027-8

I.Y. Lee, T.D. Gruber, A. Samuels, M. Yun, B. Nam, M. Kang, K. Crowley, B. Winterroth, H.I. Boshoff, C.E. Barry. Structure-activity relationships of antitubercular salicylanilides consistent with disruption of the proton gradient via proton shuttling. Bioorganic and Medicinal Chemistry 21 (2013) 114-126. https://doi.org/10.1016/j.bmc.2012.10.056 DOI: https://doi.org/10.1016/j.bmc.2012.10.056

M.J. Macielag, J.P. Demers, S.A. Fraga-Spano, D.J. Hlasta, S.G. Johnson, R.M. Kanojia, R.K. Russell, Z. Sui, M.A. Weidner-Wells, H. Werblood, B.D. Foleno, R.M. Goldschmidt, M.J. Loeloff, G.C. Webb, J.F. Barrett. Substituted salicylanilides as inhibitors of two-component regulatory systems in bacteria. Journal of Medicinal Chemistry 41 (1998) 2939-2945. https://doi.org/10.1021/jm9803572 DOI: https://doi.org/10.1021/jm9803572

N. Dasgupta, V. Kapur, K.K. Singh, T.K. Das, S. Sachdeva, K. Jyothisri, J.S. Tyagi. Characterization of a two-component system, devR-devS, of Mycobacterium tuberculosis. Tubercle and Lung Disease 80 (2000) 141-159. https://doi.org/10.1054/tuld.2000.0240 DOI: https://doi.org/10.1054/tuld.2000.0240

R.E. Moellering, B.F. Cravatt. How chemoproteomics can enable drug discovery and development. Chemical Biology 19 (2012) 11-22. https://doi.org/10.1016/j.chembiol.2012.01.001 DOI: https://doi.org/10.1016/j.chembiol.2012.01.001

K.P. Malarney, P.V. Chang. Chemoproteomic approaches for unraveling prokaryotic biology. Israel Journal of Chemistry 63 (2023) e202200076. https://doi.org/10.1002/ijch.202200076 DOI: https://doi.org/10.1002/ijch.202200076

G. Drewes, S. Knapp. Chemoproteomics and chemical probes for target discovery. Trends in Biotechnology 36 (2018) 1275-1286. https://doi.org/10.1016/j.tibtech.2018.06.008 DOI: https://doi.org/10.1016/j.tibtech.2018.06.008

L.H. Jones, H. Neubert. Clinical chemoproteomics—Opportunities and obstacles. Science Translational Medicine 9 (2017) 7951. https://doi.org/10.1126/scitranslmed.aaf7951 DOI: https://doi.org/10.1126/scitranslmed.aaf7951

X. Chen, Y.K. Wong, J. Wang, J. Zhang, Y. Lee, H. Shen, Q. Lin, Z.C. Hua. Target identification with quantitative activity based protein profiling (ABPP). Proteomics 17 (2017) 1600212. https://doi.org/10.1002/pmic.201600212 DOI: https://doi.org/10.1002/pmic.201600212

S. Wang, Y. Tian, M. Wang, M. Wang, G. Sun, X. Sun. Advanced activity-based protein profiling application strategies for drug development. Frontiers in Pharmacology 9 (2018) 353. https://doi.org/10.3389/fphar.2018.00353 DOI: https://doi.org/10.3389/fphar.2018.00353

K. Naumann. Influence of chlorine substituents on biological activity of chemicals: A review. Pest Management Science 56 (2000) 3-21. https://doi.org/10.1002/(SICI)1526-4998(200001)56:1%3C3::AID-PS107%3E3.0.CO;2-P DOI: https://doi.org/10.1002/(SICI)1526-4998(200001)56:1<3::AID-PS107>3.3.CO;2-G

W.Y. Fang, L. Ravindar, K.P. Rakesh, H.M. Manukumar, C.S. Shantharam, N.S. Alharbi, H.L. Qin. Synthetic approaches and pharmaceutical applications of chloro-containing molecules for drug discovery: A critical review. European Journal of Medicinal Chemistry 173 (2019) 117-153. https://doi.org/10.1016/j.ejmech.2019.03.063 DOI: https://doi.org/10.1016/j.ejmech.2019.03.063

M. Dolezal, J. Zitko, Z. Osicka, J. Kunes, M. Vejsova, V. Buchta, J. Dohnal, J. Jampilek, K. Kralova. Synthesis, antimycobacterial, antifungal and photosynthesis-inhibiting activity of chlorinated N-phenylpyrazine-2-carboxamides. Molecules 15 (2010) 8567-8581. https://doi.org/10.3390/molecules15128567 DOI: https://doi.org/10.3390/molecules15128567

O.S. Faleye, B.R. Boya, J.H. Lee, I. Choi, J. Lee. Halogenated antimicrobial agents to combat drug-resistant pathogens. Pharmacological Reviews 76 (2023) 90-141. https://doi.org/10.1124/pharmrev.123.000863 DOI: https://doi.org/10.1124/pharmrev.123.000863

R. Huber, L. Marcourt, M. Heritier, A. Luscher, L. Guebey, S. Schnee, E. Michellod, S. Guerrier, J.L. Wolfender, L. Scapozza, T. Kohler, K. Gindro, E.F. Queiroz.Generation of potent antibacterial compounds through enzymatic and chemical modifications of the trans-δ-viniferin scaffold. Scientific Reports 13 (2023) 15986. https://doi.org/10.1038/s41598-023-43000-5 DOI: https://doi.org/10.1038/s41598-023-43000-5

A. Krawczyk-Lebek, B. Zarowska, T. Janeczko, E. Kostrzewa-Suslow. Antimicrobial activity of chalcones with a chlorine atom and their glycosides. International Journal of Molecular Sciences 25 (2024) 9718. https://doi.org/10.3390/ijms25179718 DOI: https://doi.org/10.3390/ijms25179718

M. Perz, D. Szymanowska, T. Janeczko, E. Kostrzewa-Suslow. Antimicrobial properties of flavonoid derivatives with bromine, chlorine, and nitro group obtained by chemical synthesis and biotransformation studies. International Journal of Molecular Sciences 25 (2024) 5540. https://doi.org/10.3390/ijms25105540 DOI: https://doi.org/10.3390/ijms25105540

T.A. Taylor, C.G. Unakal. Staphylococcus aureus Infection; StatPearls Publishing, Treasure Island, FL, USA, 2024. https://www.ncbi.nlm.nih.gov/books/NBK441868 (accessed on 10 February 2025).

T. Gonec, J. Kos, M. Pesko, J. Dohanosova, M. Oravec, T. Liptaj, K. Kralova, J. Jampilek. Halogenated 1-hydroxynaphthalene-2-carboxanilides affecting photosynthetic electron transport in photosystem II. Molecules 22 (2017) 1709. https://doi.org/10.3390/molecules22101709 DOI: https://doi.org/10.3390/molecules22101709

EZChrom Elite software ver. 3.3.2. Agilent, Santa Clara, CA, USA. https://ezchrom-elite.software.informer.com/3.3/

I. Zadrazilova, S. Pospisilova, K. Pauk, A. Imramovsky, J. Vinsova, A. Cizek, J. Jampilek. In vitro bactericidal activity of 4- and 5-chloro-2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides against MRSA. BioMed Research International 2015 (2015) 349534. https://doi.org/10.1155/2015/349534 DOI: https://doi.org/10.1155/2015/349534

U. Nubel, J. Dordel, K. Kurt, B. Strommenger, H. Westh, S.K. Shukla, H. Zemlickova, R. Leblois, T. Wirth, T. Jombart, F. Balloux, W. Witte. A timescale for evolution, population expansion, and spatial spread of an emerging clone of methicillin-resistant Staphylococcus aureus. PLOS Pathogens 6 (2010) e1000855. https://doi.org/10.1371/journal.ppat.1000855 DOI: https://doi.org/10.1371/journal.ppat.1000855

G. Bosgelmez-Tinaz, S. Ulusoy, B. Aridogan, F. Coskun-Ari. Evaluation of different methods to detect oxacillin resistance in Staphylococcus aureus and their clinical laboratory utility. European Journal of Clinical Microbiology & Infectious Diseases 25 (2006) 410-412. https://doi.org/10.1007/s10096-006-0153-8 DOI: https://doi.org/10.1007/s10096-006-0153-8

F. Martineau, F.J. Picard, P.H. Roy, M. Ouellette, M.G. Bergeron. Species-specific and ubiquitous-DNA-based assays for rapid identification of Staphylococcus aureus. Journal of Clinical Microbiology 36 (1998) 618-623. https://doi.org/10.1128/jcm.36.3.618-623.1998 DOI: https://doi.org/10.1128/JCM.36.3.618-623.1998

M.P. Weinstein, J.B. Patel. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: M07-A11, 11th edition, Committee for Clinical Laboratory Standards, Wayne, PA, 2018. https://clsi.org/media/1928/m07ed11_sample.pdf

R. Schwalbe, L. Steele-Moore, A.C. Goodwin. Antimicrobial Susceptibility Testing Protocols, CRC Press, Boca Raton, FL, USA, 2007. https://doi.org/10.1201/9781420014495 DOI: https://doi.org/10.1201/9781420014495

Measuring Cell Viability/Cytotoxicity. Dojindo EU GmbH, Munich, Germany. https://www.dojindo.eu.com/Protocol/Dojindo-Cell-Proliferation-Protocol.pdf

E. Grela, J. Kozłowska, A. Grabowiecka. Current methodology of MTT assay in bacteria—A review. Acta Histochemica 120 (2018) 303-311. https://doi.org/10.1016/j.acthis.2018.03.007 DOI: https://doi.org/10.1016/j.acthis.2018.03.007

GraphPad Prism 5.00 software. GraphPadSoftware, San Diego, CA, USA. http://www.graphpad.com

Progenesis QI 4.0. Waters, Milford, USA, https://www.waters.com/nextgen/us/en/products/informatics-and-software/mass-spectrometry-software/progenesis-qi-software.html

UniProt: The Universal Protein Knowledgebase in 2023. https://www.uniprot.org/

K. Wu, S.H. Kwon, X. Zhou, C. Fuller, X. Wang, J. Vadgama, Y. Wu. Overcoming challenges in small-molecule drug bioavailability: A review of key factors and approaches. International Journal of Molecular Sciences 25 (2024) 13121. https://doi.org/10.3390/ijms252313121 DOI: https://doi.org/10.3390/ijms252313121

ACD/Percepta ver. 2012. Advanced Chemistry Development, Inc., Toronto, ON, Canada, 2012. https://www.acdlabs.com/products/percepta-platform/

C.A. Lipinski, F. Lombardo, B.W. Dominy, P.J. Feeney. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews 46 (2001) 3-26. https://doi.org/10.1016/S0169-409X(00)00129-0 DOI: https://doi.org/10.1016/S0169-409X(00)00129-0

E.H. Kerns, L. Di. Drug-Like Properties: Concepts. Structure Design and Methods: From ADME to Toxicity Optimization; Academic Press, San Diego, CA, USA, 2008. ISBN 978-0-12-369520-8

D.F. Veber, S.R. Johnson, H.Y. Cheng, B.R. Smith, K.W. Ward, K.D. Kopple. Molecular properties that influence the oral bioavailability of drug candidates. Journal of Medicinal Chemistry 45 (2002) 2615-2623. https://doi.org/10.1021/jm020017n DOI: https://doi.org/10.1021/jm020017n

T.D.Y. Chung, D.B. Terry, L.H. Smith. In vitro and in vivo assessment of ADME and PK properties during lead selection and lead optimization - guidelines, benchmarks and rules of thumb. in The Assay Guidance Manual, S. Markossian (Ed), National Institutes of Health - National Center for Advancing Translational Sciences, Rockville, MD, USA, 2015. https://www.ncbi.nlm.nih.gov/books/NBK326710/ (accessed on 08 February 2025).

C. Hansch. Bioisosterism. Intra-Science Chemistry Reports 8 (1974) 17-25.

I. Korona-Glowniak, W. Nitek, W. Tejchman, E. Zeslawska. Influence of chlorine and methyl substituents and their position on the antimicrobial activities and crystal structures of 4-methyl-1,6-diphenylpyrimidine-2(1H)-selenone derivatives. Acta Crystallographica Section C: Structural Chemistry 77 (2021) 649-658. https://doi.org/10.1107/s205322962100975x DOI: https://doi.org/10.1107/S205322962100975X

S. Janowska, J. Stefanska, D. Khylyuk, M. Wujec. The importance of substituent position for antibacterial activity in the group of thiosemicarbazide derivatives. Molecules 29 (2024) 1333. https://doi.org/10.3390/molecules29061333 DOI: https://doi.org/10.3390/molecules29061333

A. Bak, J. Kos, H. Michnova, T. Gonec, S. Pospisilova, V. Kozik, A. Cizek, A. Smolinski, J. Jampilek. Consensus-based pharmacophore mapping for new set of N-(disubstituted-phenyl)-3-hydroxyl-naphthalene-2-carboxamides. International Journal of Molecular Sciences 21 (2020), 6583. https://doi.org/10.3390/ijms21186583 DOI: https://doi.org/10.3390/ijms21186583

MetaboAnalyst 6.0. https://dev.metaboanalyst.ca/MetaboAnalyst/upload/StatUploadView.xhtml

Staphylococcus aureus subsp. aureus Mu50 (MRSA/VISA): SAV1363. DBGET Search, Kyoto University Bioinformatics Center. https://www.genome.jp/entry/sav:SAV1363

B. Couvreur, R. Wattiez, A. Bollen, P.l. Falmagne, D. Le Ray, J.C. Dujardin. Eubacterial HslV and HslU subunits homologs in primordial eukaryotes. Molecular Biology and Evolution 19 (2002) 2110-2117. https://doi.org/10.1093/oxfordjournals.molbev.a004036 DOI: https://doi.org/10.1093/oxfordjournals.molbev.a004036

F. Zhang, W. Cheng. The mechanism of bacterial resistance and potential bacteriostatic strategies. Antibiotics 11 (2022) 1215. https://doi.org/10.3390/antibiotics11091215 DOI: https://doi.org/10.3390/antibiotics11091215

F.G. Avci. Unraveling bacterial stress responses: implications for next-generation antimicrobial solutions. World J Microbiol Biotechnol 40 (2024) 285. https://doi.org/10.1007/s11274-024-04090-z DOI: https://doi.org/10.1007/s11274-024-04090-z

B. Zavizion, Z. Zhao, A. Nittayajarn, R.J. Rieder. Rapid microbiological testing: monitoring the development of bacterial stress. PLoS One 5 (2010) e13374. https://doi.org/10.1371/journal.pone.0013374 DOI: https://doi.org/10.1371/journal.pone.0013374