Abstract
Eleven novel imide-tetrazoles were synthesized. In the initial stage of research, in silico structure-based pharmacological prediction was conducted. All compounds were screened for antimicrobial activity using standard and clinical strains. Within the studied group, compounds 1–3 were recognized as leading structures with the most promising results in antimicrobial studies. Minimal inhibitory concentration values for compounds 1, 2, 3 were within the range of 0.8–3.2 μg/mL for standard and clinical Gram-positive and Gram-negative bacterial strains, showing in some cases higher activity than the reference Ciprofloxacin. Additionally, all three inhibited the growth of all clinical Staphylococci panels: Staphylococcus aureus (T5592; T5591) and Staphylococcus epidermidis (5253; 4243) with MIC values of 0.8 μg/mL. Selected compounds were examined in topoisomerase IV decatenation assay and DNA gyrase supercoiling assay, followed by suitable molecular docking studies to explore the possible binding modes. In summary, the presented transition from substrate imide-thioureas to imide-tetrazole derivatives resulted in significant increase of antimicrobial properties. The compounds 1–3 proposed here provide a promising basis for further exploration towards novel antimicrobial drug candidates.
Highlights
IntroductionAntibiotic resistance is mentioned as one of the most important health threats of present times
Introduction published maps and institutional affilAntibiotic resistance is mentioned as one of the most important health threats of present times
The transition presented here from imide-thiourea substrates, thoroughly studied in our previous works [22,23,24,25], to appropriate novel imide-tetrazole products was successfully performed in the course of a single reaction
Summary
Antibiotic resistance is mentioned as one of the most important health threats of present times. Increasing appearance of multi-drug-resistant organisms outside the hospital environment confirms their presence in our everyday life. The situation is worsening due to the lack of effective new antimicrobial molecules, and the inappropriate use of available antibiotics. Clinicians have limited appropriate therapeutic options for infected patients [1]. We can divide resistance mechanisms into two general categories, internal and acquired. Internal resistance mechanisms are most often associated with chromosomal coding
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