Biophysical Society Thematic Meeting | Stockholm 2022

Physical and Quantitative Approaches to Overcome Antibiotic Resistance

Poster Abstracts

25-POS Board 25 ENZYMATIC SYNTHESIS AND CHARACTERIZATION OF ARYL IODIDES OF SOME PHENOLIC ACIDS WITH ENHANCED ANTIBACTERIAL PROPERTIES Ewa Olchowik-Grabarek 1 ; Frédérique Mies 2 ; Szymon Sekowski 1 ; Alina T Dubis 3 ; Pascal Laurent 4 ; Maria V Zamaraeva 1 ; Izabela Swiecicka 1 ; Vadim Shlyonsky 2 ; 1 University of Bialystok, Laboratory of Molecular Biophysics, Department of Microbiology and Biotechnology, Faculty of Biology, Bialystok, Poland 2 Université libre de Bruxelles, Laboratory of Physiology and Pharmacology, Faculty of Medicine, Bruxelles, Belgium 3 University of Bialystok, Department of Organic Chemistry, Faculty of Chemistry, Bialystok, Poland 4 Université libre de Bruxelles, Laboratory of Chemistry Instruction, Faculty of Medicine, Bruxelles, Belgium Phenolic acids represent a class of drugs with mild antibacterial properties. We have synthesized iodinated gallic and ferulic acids and together with commercially available iodinated forms of salicylic acids studied their cytotoxicity, bacteriostatic and anti-virulence action. Out of these, iodogallic acid had lowest minimal inhibitory concentration against S. aureus (MIC=0.4 mM/118.8 µg/ml). At non-bacteriostatic and non-cytotoxic concentrations (<0.1 mM), it had strongest effect on erythrocyte membrane lipid ordering (at concentrations below 10 µM) and on α -hemolysin secretion by the bacteria (at a concentration of 40 µM). It formed strong complexes with α -hemolysin in solutions (logKb =4.68±0.60) and, accordingly, inhibited its nano-pore conduction in artificial lipid bilayers (IC50=37.9±5.3 µM). These effects of iodogallic acid converged on prevention of hemolysis induced by α -hemolysin (IC50= 41.5±4.2 µM) and point to enhanced and diverse antivirulence properties of iodinated aryl iodides. The analysis of molecular surface electrostatic charge distribution, molecular hydrophilicity, electronegativity and dipole moment of selected compounds suggests the importance of the number of hydroxyl groups and their proximity to iodine. A particular electrostatic surface charges modification in iodogallic acid led to higher electrostatic hydrophilicity, while it preserved at the same the overall molecular electronegativity and dipole moment as in non-iodinated gallic acid. This study may show new directions for the development of antibacterial/antivirulence therapeutics.

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