Antimicrobial activities and mode of action of the selected novel thienopyrimidines derivatives (compound no.20)

Abstract

Background and purpose: Although thienopyrimidines have an important antimicrobial efficacy, there is still a lack of understanding their antimicrobial mode of action. The current study aims to assess the antimicrobial activity of newly synthesized thienopyrimidines derivatives against some pathogens and to determine the mode of action of the most potent compound (compound no. 20).

Materials and methods: Newly synthesized thieno[2,3-d]pyrimidinediones compounds   examined for antimicrobial activity against pathogenic organisms by cut plug and viable cell counting methods. The minimum inhibitory concentration (MIC) of (compound no. 20), it's mode of action; cytotoxicity and LC₅₀ were determined. 

Results One compound (compound no. 20) displayed potent activity. The growth inhibitory effect (M/C) of (compound no. 20) differed among the tested strains. The inhibition becomes stronger; Candida albicans> Escherichia coli> Staphylococcus aureus. The MIC for all the tested microorganisms was > 50 <100 μg/mL. E. coli and C. albicans recorded highest value of potassium flow. Compound no. 20 affects oxygen consumption and exhibited cytotoxicity against E. coli. LC50 value with brine shrimps was estimated at 49.114 µg/mL concentration. Conclusion: It could be concluded that the mode of action of compound no.20 may be due to disruption of the cytoplasmic membrane by action upon the membrane potentials, permeability or net surface charge of the microbial membranes by its physicochemical characteristic. This led to leakage of cellular components and eventually cell death. This will lead to improved antimicrobial formulations and to ensure the prevention of the emergence of microbial resistance.