Antistaphylococcal Activities and ADME-Related Properties of Chlorinated Arylcarbamoylnaphthalenylcarbamates

0558879 - ÚVGZ 2023 RIV CH eng J - Journal Article
Gonec, T. - Pindjakova, D. - Vrablova, L. - Strharsky, T. - Michnova, H. - Kauerová, T. - Kollár, P. - Oravec, Michal - Jendrzejewska, I. - Čížek, A. - Jampílek, J.
Antistaphylococcal Activities and ADME-Related Properties of Chlorinated Arylcarbamoylnaphthalenylcarbamates.
Pharmaceuticals. Roč. 15, č. 6 (2022), č. článku 715. E-ISSN 1424-8247
R&D Projects: GA MŠMT(CZ) LM2018123; GA MŠMT(CZ) EF16_019/0000797
Institutional support: RVO:86652079
Keywords : antimicrobial activity * staphylococcus-aureus * biological-activity * resistance * derivatives * permeability * mechanisms * spectrum * design * oxides * hydroxynaphthalenes * carbamates * antistaphylococcal activity * cytotoxicity * lipophilicity * structure-activity relationships
OECD category: Pharmacology and pharmacy
Impact factor: 4.6, year: 2022
Method of publishing: Open access
https://www.mdpi.com/1424-8247/15/6/715

Pattern 1-hydroxy-N-(2,4,5-trichlorophenyl)-2-naphthamide and the thirteen original carbamates derived from it were prepared and characterized. All the compounds were tested against Staphylococcus aureus ATCC 29213 as a reference and quality control strain and in addition against three clinical isolates of methicillin-resistant S. aureus (MRSA). Moreover, the compounds were evaluated against Enterococcus faecalis ATCC 29212, and preliminary in vitro cytotoxicity of the compounds was assessed using the human monocytic leukemia cell line (THP-1). The lipophilicity of the prepared compounds was experimentally determined and correlated with biological activity. While pattern anilide had no antibacterial activity, the prepared carbamates demonstrated high antistaphylococcal activity comparable to the used standards (ampicillin and ciprofloxacin), which unfortunately were ineffective against E. feacalis. 2-[(2,4,5-Trichlorophenyl)carba- moyl]naphthalen-1-yl ethylcarbamate (2) and 2-[(2,4,5-trichlorophenyl)carbamoyl]naphthalen-1-yl butylcarbamate (4) expressed the nanomolar minimum inhibitory concentrations (MICs 0.018-0.064 mu M) against S. aureus and at least two other MRSA isolates. Microbicidal effects based on the minimum bactericidal concentrations (MBCs) against all the tested staphylococci were found for nine carbamates, while 2-[(2,4,5-trichlorophenyl)carbamoyl]naphthalen-1-yl heptylcarbamate (7) and 2-[(2,4,5-trichlorophenyl)carbamoyl]naphthalen-1-yl (4-phenylbutyl)carbamate (14) demonstrated MBCs in the range of 0.124-0.461 mu M. The selectivity index (SI) for most investigated carbamates was >20 and for some derivatives even >100. The performed tests did not show an effect on the damage to the bacterial membrane, while the compounds were able to inhibit the respiratory chain of S. aureus.
Permanent Link: http://hdl.handle.net/11104/0332380