Insights into biological activity of ureidoamides with primaquine and amino acid moieties

J Enzyme Inhib Med Chem. 2018 Dec;33(1):376-382. doi: 10.1080/14756366.2017.1423067.

Abstract

Primaquine (PQ) ureidoamides 5a-f were screened for antimicrobial, biofilm eradication and antioxidative activities. Susceptibility of the tested microbial species towards tested compounds showed species- and compound-dependent activity. N-(diphenylmethyl)-2-[({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]-4-methylpentanamide (5a) and 2-(4-chlorophenyl)-N-(diphenylmethyl)-2-[({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]acetamide (5d) showed antibacterial activity against S. aureus strains (MIC = 6.5 µg/ml). Further, compounds 5c and 5d had weak antibacterial activity against Escherichia coli and Pseudomonas aeruginosa. None of the tested compounds showed a wide spectrum of antifungal activity. In contrast, most of the compounds exerted strong activity in a biofilm eradication assay against E. coli, P. aeruginosa and Candida albicans, comparable to or even higher than gentamycin, amphotericin B or parent PQ. The most active compounds were 5a and 5b. Tested compounds were inactive against biofilm formation by C. parapsylosis, Enterococcus faecalis, C. tropicalis and C. krusei. Compounds 5b-f significantly inhibited lipid peroxidation (80-99%), whereas compound 5c presented interesting LOX inhibition.

Keywords: Primaquine; antibacterial activity; antioxidative screening; biofilm eradication; ureidoamide.

MeSH terms

  • Amides / chemistry
  • Amides / pharmacology*
  • Amino Acids / chemistry
  • Amino Acids / pharmacology*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Biofilms / drug effects
  • Candida albicans / drug effects
  • Dose-Response Relationship, Drug
  • Escherichia coli / drug effects
  • Glycine max / enzymology
  • Humans
  • Lipid Peroxidation / drug effects
  • Lipoxygenase / metabolism
  • Lipoxygenase Inhibitors / chemistry
  • Lipoxygenase Inhibitors / pharmacology
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Primaquine / chemistry
  • Primaquine / pharmacology*
  • Pseudomonas aeruginosa / drug effects
  • Structure-Activity Relationship

Substances

  • Amides
  • Amino Acids
  • Anti-Bacterial Agents
  • Antifungal Agents
  • Antioxidants
  • Lipoxygenase Inhibitors
  • Lipoxygenase
  • Primaquine

Grants and funding

Support for this study by the Croatian Science Foundation (project number IP-2014–09-1501) is gratefully acknowledged.