Design, synthesis, docking studies and antibiotic evaluation (in vitro) of some novel (E)-4-(3-(diphenylamino)phenyl)-1-(4-methoxyphenyl)-2-methylbut-3-en-1-one and their analogues
Authors: Tukur AbdulRazaq , Habila James Dama , Ayo Rachael Gbekele-Oluwa , Iyun Ogunkemi Risikat Agbeke 
Published: March 2022

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 obtain eight novel triphenylamine chalcones. The compound’s antimicrobial properties were investigated (in vitro). With the non-mutant X-ray Human cytochrome P450 21A2 Hydroxyprogesterone retrieved from Protein Data Bank (PDB: 5VBU), molecular docking experiments were also carried out to analyse the most favourable conformation and find the orientation that maximizes interaction and minimize energy.

Results

Eight novel triphenylamine chalcones were successfully synthesized and recrystallized using ethanol, the percentage yield of the compounds were between 30 and 92%. The activity against different pathogens revealed that, all synthesized compounds showed marked antimicrobial activity against the tested microorganisms. (E)-3-(4-(diphenylamino)phenyl)-1-(3′-nitrophenyl)prop-2-en-1-one (1b) showed the highest zone of inhibition against Aspergillus niger, measuring 30 mm. The minimum inhibitory concentration (MIC) results revealed that (E)-1-(4′-bromophenyl)-3-(4-(diphenylamino)phenyl)prop-2-en-1-one (1a), (E)-3-(4-(diphenylamino)phenyl)-1-(3′-nitrophenyl)prop-2-en-1-one (1b), (E)-1-(4′-chlorophenyl)-3-(4-diphenylamino)phenyl)prop-2-en-1-one (1c), (E)-3-(4-diphenylamino)phenyl)-1-(4′-fluorophenyl)prop-2-en-1-one (1d) and (E)-4-(3-(diphenylamino)phenyl)-1-(4-fluorophenyl)-2-methylbut-3-en-1-one (2d) had the lowest MIC and inhibit Aspergillus niger growth at 12.5 µg/ml. All the synthesized compounds showed minimum bactericidal concentration and minimum fungicidal concentration (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 Human cytochrome P450 21A2 Hydroxyprogesterone (PDB: 5VBU) reveal that the binding affinity of the synthesized chalcones was 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.

Conclusions

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, respectively. Therefore, displayed better antifungal potential as compared to the rest of the compounds. The outcome of the docking analysis revealed that (E)-4-(3-(diphenylamino)phenyl)-1-(4′-hydroxyphenyl)-2-methylbut-3-en-1-one (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).