title: Synthesis of Cyclic Imides (Methylphtalimides, Carboxylic Acid Phtalimides and Itaconimides) and Evaluation of their Antifungal Potential.
abstract: BACKGROUND
  This paper describes the synthesis of three different subfamilies of cyclic imides: methylphtalimides, carboxyl acid phtalimides and itaconimides.
  
  
  METHODS
  Fifteen compounds (five of each sub-family) were obtained by the reaction of appropriated anhydrides and different aromatic amines, using the manual Topliss method. Their structures were confirmed by spectral data (IR and NMR). The antifungal activity of the synthesized compounds was investigated by broth microdilution to determine the minimal inhibitory concentration (MIC). The ability to inhibit the biofilm formation or destroy mature Candida albicans biofilm was also evaluated for the most active substances.
  
  
  RESULTS
  The results indicated that only the itaconimides 11-15 exhibited potent and promising antifungal properties, with MIC100 between 1 and 64 μg mL-1, being several times more potent than the reference drug, Fluconazole. Compounds 11-15 inhibited between 64% and 95% of biofilm formation, and destroyed between 78% and 99% of mature biofilm at a concentration of 64 μg mL-1. ADME (absorption, distribution, metabolism and excretion) in silico evaluations were carried out to predict whether the molecules under study are good drug candidates.
  
  
  CONCLUSIONS
  Itaconimides appear to be promising and relevant as tools for the future development of new and effective medicinal agents to treat fungal diseases.
authors.forename: Dorimar
authors.initials: D
authors.lastname: Stiz
authors.forename: Rogério
authors.initials: R
authors.lastname: Corrêa
authors.forename: Felicia D
authors.initials: FD
authors.lastname: D'Auria
authors.forename: Giovanna
authors.initials: G
authors.lastname: Simonetti
authors.affiliation: Universidade do Vale do Itajaí (UNIVALI), Caixa Postal 360 - CEP 88302-202 - Itajaí - Santa Catarina - Brazil. cechinel@univali.br.
authors.forename: Valdir
authors.initials: V
authors.lastname: Cechinel-Filho
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D003198:Computer Simulation; D015725:Fluconazole / Q000494:pharmacology; D003904:Mitosporic Fungi / Q000187:drug effects; D010797:Phthalimides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D010797:Phthalimides; D013388:Succinimides; D015725:Fluconazole