1. Antimicrobial, Cytotoxic and Mutagenic Activity of Gemini QAS Derivatives of 1,4:3,6-Dianhydro-l-iditol.
- Author
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Sikora K, Nowacki A, Szweda P, Woziwodzka A, Bartoszewska S, Piosik J, and Dmochowska B
- Subjects
- Anti-Infective Agents chemical synthesis, Anti-Infective Agents chemistry, Anti-Infective Agents pharmacology, Candida albicans, Cytotoxins chemical synthesis, Cytotoxins chemistry, Cytotoxins pharmacology, Escherichia coli, HaCaT Cells, Humans, Microbial Sensitivity Tests, Mutagenicity Tests, Mutagens chemical synthesis, Mutagens chemistry, Mutagens pharmacology, Staphylococcus aureus, Sugar Alcohols chemical synthesis, Quaternary Ammonium Compounds chemical synthesis, Quaternary Ammonium Compounds chemistry, Quaternary Ammonium Compounds pharmacology, Sugar Alcohols chemistry, Sugar Alcohols pharmacology
- Abstract
A series of quaternary diammonium salts derivatives of 1,4:3,6-dianhydro-l-iditol were synthesized, using isommanide (1,4:3,6-dianhydro-d-mannitol) as a starting material. Both aromatic (pyridine, 4-( N , N -dimethylamino)pyridine (DMAP), (3-carboxamide)pyridine; N -methylimidazole) and aliphatic (trimethylamine, N , N -dimethylhexylamine, N , N -dimethyloctylamine, N , N -dimethyldecylamine) amines were used, giving eight gemini quaternary ammonium salts (QAS). All salts were tested for their antimicrobial activity against yeasts, Candida albicans and Candida glabrata , as well as bacterial Staphylococcus aureus and Escherichia coli reference strains. Moreover, antibacterial activity against 20 isolates of S. aureus collected from patients with skin and soft tissue infections ( n = 8) and strains derived from subclinical bovine mastitis milk samples ( n = 12) were evaluated. Two QAS with octyl and decyl residues exhibited antimicrobial activity, whereas those with two decyl residues proved to be the most active against the tested pathogens, with MIC of 16-32, 32, and 8 µg/mL for yeast, E. coli, and S. aureus reference and clinical strains, respectively. Only QAS with decyl residues proved to be cytotoxic in MTT assay against human keratinocytes (HaCaT), IC
50 12.8 ± 1.2 μg/mL. Ames test was used to assess the mutagenic potential of QAS, and none of them showed mutagenic activity in the concentration range 4-2000 µg/plate.- Published
- 2022
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