Abstract

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 investigated (In-vitro). With the non-mutant 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 minimize energy. Eight novel triphenylamine chalcones were successfully synthesized and recrystallized using ethanol, the percentage yield of the compounds were between 30 – 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 against Aspergillus niger, measuring 30 mm.. The minimum concentration inhibitory concentration (MIC) results revealed that, compounds 1a, 1b, 1c, 1d, and 2d had the lowest MIC and inhibit Aspergillus niger growth at 12.5 g/ml. All the synthesized compounds showed an MBC/MFC effect against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Candida albicans and Aspergillus niger at 50 µg/ml. The docking studies of the synthesized chalcones with the binding site of the target receptor, reveals that the binding affinity of the synthesized chalcones were in the range of -11.2 to -9.4 kcal/mol and, showed 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. 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 against Aspergillus niger. Therefore, displayed 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.

Key words: Chalcones, triphenylamine, Claisen-Schmidt condensation, anti-microbial activity, molecular docking, binding affinity