The present work aims to synthesize four series of phenothiazine incorporation Mannich bases. Therefore, 10-methyl-10H-phenothiazine-3-sulfonamide (4) which was subjected to react with some secondary amines and formaldehyde to give the Mannich bases 5a-f, and 6-13. Compound 13 was then subjected to react with some secondary amines and formaldehyde to give the corresponding Mannich bases 14a-f. In total, twenty-two new compounds were synthesized and evaluated for in vitro growth inhibition activity against P. aeruginosa, E. coli, and S. aureus. Among the tested compounds, compounds 3, 5a, 5c, 6, 12, 13, 14d, and 14e exhibited good activity with a MIC value (12.5 μg/mL), compounds 5b, 10, 11, 14a, and 14c exhibited strong activity against the growth of S. aureus with a MIC value (6.25 μg/mL), and compound 14b superior against S. aureus with a MIC value (3.125 μg/mL) compared to drug reference ciprofloxacin with MIC value (2 μg/mL). The molecular docking investigation revealed the presence of many derivatives with high binding affinities and distinct interaction patterns with the target protein. Derivatives 14a-e emerged as the most promising possibilities, displaying the greatest binding energies and a varied variety of interaction types, including hydrogen bonding and pi interactions, over different distances, with derivative 14b exhibiting the highest binding energy at S = -8.3093 kcal/mol. These derivatives displayed superior binding affinities and various interaction mechanisms with the target protein, suggesting that they have great promise as lead compounds for future development into therapeutic medicines.

	Year	Citations

About