The Evaluation of DHPMs as Biotoxic Agents on Pathogen Bacterial Membranes

Barbara Gawdzik; Paweł Kowalczyk; Dominik Koszelewski; Anna Brodzka; Joanna Masternak; Karol Kramkowski; Aleksandra Wypych; Ryszard Ostaszewski

doi:10.3390/membranes12020238

The Evaluation of DHPMs as Biotoxic Agents on Pathogen Bacterial Membranes

Membranes (Basel). 2022 Feb 18;12(2):238. doi: 10.3390/membranes12020238.

Authors

Barbara Gawdzik¹, Paweł Kowalczyk², Dominik Koszelewski³, Anna Brodzka³, Joanna Masternak¹, Karol Kramkowski⁴, Aleksandra Wypych⁵, Ryszard Ostaszewski³

Affiliations

¹ Institute of Chemistry, Jan Kochanowski University, Uniwersytecka 7, 25-406 Kielce, Poland.
² Department of Animal Nutrition, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3, 05-110 Jabłonna, Poland.
³ Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
⁴ Department of Physical Chemistry, Medical University of Bialystok, Kilińskiego 1 Str., 15-089 Białystok, Poland.
⁵ Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University in Torun, ul. Wileńska 4, 87-100 Toruń, Poland.

Abstract

Herein, we present biological studies on 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) obtained via Biginelli reaction catalyzed by NH4Cl under solvent-free conditions. Until now, DHPMs have not been tested for biological activity against pathogenic E. coli strains. We tested 16 newly synthesized DHPMs as antimicrobial agents on model E. coli strains (K12 and R2-R4). Preliminary cellular studies using MIC and MBC tests and digestion of Fpg after modification of bacterial DNA suggest that these compounds may have greater potential as antibacterial agents than typically used antibiotics, such as ciprofloxacin (ci), bleomycin (b) and cloxacillin (cl). The described compounds are highly specific for pathogenic E. coli strains based on the model strains used and may be engaged in the future as new substitutes for commonly used antibiotics in clinical and nosocomial infections in the pandemic era.

Keywords: 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) obtained by Biginelli reaction; DNA-N-glycosylase; Fpg protein formamidopyrimidine; lipopolysaccharide (LPS).