Insight into antimicrobial activity of substituted phenylcarbamoyloxypiperazinylpropanols

POSPISILOVA, S., I. MALIK, J. CURILLOVA, H. MICHNOVA, L. CERNA, Tereza PADRTOVÁ, J. HOSEK, D. PECHER, A. CIZEK and J. JAMPILEK. Insight into antimicrobial activity of substituted phenylcarbamoyloxypiperazinylpropanols. Bioorganic Chemistry. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE, 2020, vol. 102, SEP 2020, p. 1-13. ISSN 0045-2068. Available from: https://dx.doi.org/10.1016/j.bioorg.2020.104060.

Basic information

• Original name: Insight into antimicrobial activity of substituted phenylcarbamoyloxypiperazinylpropanols
• Authors: POSPISILOVA, S., I. MALIK, J. CURILLOVA, H. MICHNOVA, L. CERNA, Tereza PADRTOVÁ (203 Czech Republic, belonging to the institution), J. HOSEK, D. PECHER, A. CIZEK and J. JAMPILEK.
• Edition: Bioorganic Chemistry, SAN DIEGO, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2020, 0045-2068.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30104 Pharmacology and pharmacy
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 5.275
• RIV identification code: RIV/00216224:14160/20:00118183
• Organization unit: Faculty of Pharmacy
• Doi: http://dx.doi.org/10.1016/j.bioorg.2020.104060
• UT WoS: 000567809600011
• Keywords in English: Piperazine; Carbamate; Antibacterial; Antimycobacterial; Synergy; Antibiofilm activity; Antiproliferative effect
• Tags: rivok, ÚChL
• Tags: International impact, Reviewed

Abstract

3-[4-(Substituted)phenyl-/4-(diphenylmethyl)phenylpiperazin-1-yl]-2-hydroxypropyl-1-[(substituted)phenyl] carbamates and their salts with hydrochloric acid were synthesized, characterized, and tested in vitro against Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 as reference and quality control strains, against three methicillin-resistant isolates of S. aureus, and three isolates of vancomycin-resistant E. faecalis. All the compounds were evaluated against Mycobacterium tuberculosis H37Ra/ATCC 25177, M. kansasii DSM 44162, and M. smegmatis ATCC 700084. All of the tested compounds demonstrated very good activity against all the tested strains/isolates comparable with or better than that of clinically used drugs (ampicillin, ciprofloxacin, vancomycin, isoniazid). 1-[{(3-Trifluoromethyl)phenyl}carbamoyloxy-2-hydroxypropyl]-4-(3,4-dichlorophenyl)piperazin-1-ium chloride demonstrated the highest potency against all the tested strains/isolates (MICs ranged from 3.78 to 30.2 mu M), and 1-[{(3-trifluoromethyl)phenyl}carbamoyloxy-2-hydroxypropyl]-4-(diphenylmethyl)piperazin-1-ium chloride was the most effective against all the screened mycobacterial strains (MICs ranged from 3.64 to 14.5 mu M). All the investigated derivatives had strong antibiofilm activity against S. aureus ATCC 29123 and a synergistic or additive effect with gentamicin against isolates of E. faecalis with both intrinsic and acquired resistance to gentamicin. The screening of the cytotoxicity of the compounds was performed using human monocytic leukemia THP-1 cells. The IC50 values of the most effective compounds ranged from ca. 2.8 to 7.3 mu M; thus, it can be stated that the antimicrobial effect is closely connected with their cytotoxicity. These observations disqualify these compounds from further development as antimicrobial agents, but they can be considered potential multi-target drugs with a preferred anticancer effect with good water solubility and additional anti-infectious activity.