Design, synthesis, docking studies, and antibiotic evaluation (in vitro) of some novel triphenylamine chalcones and their analogues

Abstract

Background: Antibiotic resistance has risen as a result of a variety of conditions, prompting 
researchers to look for new compounds that can combat multidrug-resistant organisms. 
Over the last two decades, chalcones have been proved to be attractive moieties in drug 
discovery. Various substituted acetophenones, propiophenones, and 4-(diphenylamino)
benzaldehyde were combined, using the aldol condensation reaction to obtained eight 
novel triphenylamine chalcones. The compound’s antimicrobial properties were investi
gated (in vitro). With the nonmutant X-ray target receptor (PDB: 5VBU), molecular docking 
experiments were also carried out to analyze the most favorable conformation and find 
the orientation that maximizes interaction and minimizes energy.
Results: Eight novel triphenylamine chalcones were successfully synthesized and recrys
tallized using ethanol; the percentage yield of the compounds was between 30% and 
92%. The activity against different pathogens revealed that all synthesized compounds 
showed marked antimicrobial activity against the tested microorganisms. Compound 1b 
showed the highest zone of inhibition (ZOI) against Aspergillus niger, measuring 30 mm. 
The minimum inhibitory concentration (MIC) results revealed that compounds 1a–1d, and 
2d had the lowest MIC and inhibited A. niger growth at 12.5 g/ml. All the synthesized 
compounds showed a minimum bactericidal/fungicidal concentration (MBC/MFC) effect 
against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Candida albicans, and 
A. niger at 50 µg/ml. The docking studies of the synthesized chalcones with the binding 
site of the target receptor reveal that the binding affinity of the synthesized chalcones was 
in the range of −11.2 to −9.4 kcal/mol, and showed the highest binding score compared 
to that of the standard drugs (fluconazole and ciproflaxacin), with docking scores of −7.9 
and −7.3 kcal/mol, respectively.
Conclusion: The investigation reveals that compound 1b showed the highest ZOI of 30 
mm, least MIC, and MBC/MFC of 12.5 and 50 µg/ml, respectively, against A. niger, there
fore displaying better antifungal potential as compared to the rest of the compounds. The 
outcome of the docking analysis revealed that compound 2a showed a better binding 
affinity of −11.2 kcal/mol, which is higher than the remaining compounds and the control 
drugs (fluconazole and ciproflaxacin). Therefore, compounds 1b and 2a, which showed 
better antifungal and highest binding affinity, could be potential candidates in drug design.