Antimicrobial, Cytotoxic and Mutagenic Activity of Gemini QAS Derivatives of 1,4:3,6-Dianhydro-l-iditol.

Karol Sikora,Jacek Piosik,Anna Woziwodzka,Andrzej Nowacki,Sylwia Bartoszewska,Barbara Dmochowska,Piotr Szweda

doi:10.3390/molecules27030757

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), IC50 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.

Highlights

Rising consumption, depleting fossils fuels, and environmental challenges are motivating chemists, biologists, and biotechnologists to search for new chemicals derived from renewable resources
All gemini quaternary ammonium salts were prepared in a two-step synthesis
The antimicrobial potential of the tested agents was evaluated against two reference strains of bacteria: Staphylococcus aureus ATCC 25923 and Escherichia coli K12, two reference strains of pathogenic yeasts, Candida albicans ATCC10231 and Candida glabrata DSMZ11226, as well as 20 strains of clinical 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)

Summary

Introduction

Rising consumption, depleting fossils fuels, and environmental challenges are motivating chemists, biologists, and biotechnologists to search for new chemicals derived from renewable resources. Except for new compounds with superior properties, a search for alternative ways of obtaining crucial chemicals is an important issue. The most prominent renewable resource is biomass; it can be used both as a source of energy and a wide variety of chemicals. Sugars, alditols, and anhydroalditols can be generated in large quantities by biomass processing, making it a convenient platform for the synthesis of new active compounds [1,2,3]. It was established that sugars are the energy source for living organisms. They are important building blocks of many organisms forming cellulose, chitin, DNA, and RNA. Glycocalyx, the sugar outer layer of cells, protects them from external conditions and enables red blood cells to pass through capillary vessels [6,7]

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