Novel N-Cycloalkylcarbonyl-N'-arylthioureas: Synthesis, Design, Antifungal Activity and Gene Toxicity

Chem Biodivers. 2020 Jul;17(7):e2000212. doi: 10.1002/cbdv.202000212. Epub 2020 Jun 23.

Abstract

A synthesis method of novel N-cycloalkylcarbonyl-N'-arylthioureas was developed. It consists of sequential addition of equimolecular amounts of ammonium isothiocyanate and substituted anilines to cycloalkylcarbonyl chlorides. The identity and purity of products were confirmed by LC/MS spectra, their structure by elemental analysis, IR and 1 H-NMR spectra. Preliminary antimicrobial screening for standard microorganisms and molecular docking allowed to select several structures for antifungal and genetic toxicity studies. Conducted in vitro screening of 9 compounds for antifungal potential against 11 phytopathogenic fungi and three Phytophthora strains revealed that two N-(arylcarbamothioyl) cyclopropanecarboxamides at a concentration of 50 μg/ml exhibited activities comparable to the standard antifungal agent 'Cyproconazole'. Analysis of mutagenicity of novel thioureas using the Salmonella reverse mutagenicity assay ('Ames Test') showed a low gene-toxicity profile.

Keywords: N-cycloalkylcarbonyl-N′-arylthioureas; gene toxicity; mutagenicity; spectral data, anti-phytopathogens; synthesis.

MeSH terms

  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Fungi / drug effects*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Salmonella / genetics
  • Structure-Activity Relationship
  • Thiourea / chemical synthesis
  • Thiourea / chemistry
  • Thiourea / pharmacology*

Substances

  • Antifungal Agents
  • Thiourea