Cleaner approach and antimicrobial screening of 2-selenoacetanilides: emergence of potential agents against co-infection

Abstract

Motivated to expand the investigation of the antimicrobial profile of 2-selenocetanilides and ebselen analogue, four compounds were prepared using a cleaner method in water as a solvent. Thus, 2-selenoacetanilides were obtained by the alkylation reaction of 2-chloroacetanilides with benzoyl (or phthalylglycyl) selenoate generated in situ under mild conditions. New compound 3a was submitted to single crystal X-ray diffraction, where only the Z-conformer was observed. In silico ADMET test was required to predicate the drug-like character of 2-selenoacetanilides, where, with exception of substituted 2-selenocetanilides that are probably mutagenic, all compounds predicted positive characteristics of lipophilicity, absorption, solubility and toxicity. Antimicrobial search for 2-selenoacetanilides was expanded, showing activity against 10 of 15 microorganisms tested, with MICs ≤ 80 µg.mL⁻¹, including a medium pathogen (Cryptococcus gattii), high pathogens (Candida glabrata and C. tropicalis), a critical pathogen (Aspergillus fumigatus), in addition to Klebsiella pneumoniae, known as a superbug. The results indicate the emergence of compound 3a as a potential fungicidal against C. gattii, with MIC/MFC of 2.5 µg.mL⁻¹, in comparison to the standard drug fluconazole, as well as compound 4c as a potential antimicrobial against K. pneumoniae and C. gattii, with MIC/MBC/MFC of 10 µg.mL⁻¹, i.e. a new candidate to combat co-infection.