Synthesis, antimicrobial evaluation, ADMET prediction, molecular docking and dynamics studies of pyridine and thiophene moiety-containing chalcones

In this study, three pyridine- and four thiophene-containing chalcone derivatives were synthesized via Claisen-Schmidt condensation reaction, where five derivatives were new. Different spectral analyses (IR, 1H NMR, HRMS) clarified the structures and these proposed compounds were screened for antimicrobial activity by the agar disc diffusion technique. Compound 1c was conspicuously active against most of the bacterial and fungal strains. It displayed higher activity against Bacillus cereus (22.3 +/- 0.6 mm), Shigella sonnei (43.3 +/- 0.6 mm) and Shigella boydii (34.0 +/- 1.0 mm) compared to the standard ceftriaxone (20.3 +/- 0.6 mm, 40.3 +/- 0.6 mm and 25.7 +/- 0.6 mm, respectively). In addition, the exhibited inhibition zone of compound 1c against all fungal strains was higher than that of the standard amphotericin B. All the newly synthesized derivatives satisfied the ADME properties, and no toxicological risks were found. All compounds were docked against three protein receptors with the range of binding affinity of -6.3 to -9.6 kcal mol-1. Molecular dynamics simulation was scrutinized further for compound 1c in three protein-ligand complexes where root mean square deviation and root mean square fluctuation data were below 2 & Aring;, proposing its stability inside and minimal structural changes.