Phenothiazine derivatives: Synthesis, docking studies and antimicrobial activity

•Novel hybrid phenothiazine moiety was synthesized.•Antimicrobial effectiveness of five phenothiazine derivatives, namely A, B, C, D and E, was examined.•Molecular docking studies provided additional evidence of the ability of these four derivatives to bind with the target enzyme PBP2a.•Compound E is the most active antibacterial candidate against Pseudomonas aeruginosa with 330% in comparison with the reference drug penicillin 10 The antimicrobial effectiveness of five phenothiazine derivatives, namely A, B, C, D and E, was examined against three Gram-positive and three Gram-negative bacteria, as well as seven fungal species. Analysis of the gathered data revealed that all derivatives exhibited strong antibacterial properties. However, their performance as antifungal agents were comparatively less effective which may be attributed to cell structure of fungi. Notably, in several instances, the activity of the phenothiazine derivatives surpassed that of the reference drug penicillin 10. Furthermore, molecular docking studies provided additional evidence of the ability of these four derivatives to bind with the target enzyme PBP2a. The docking scores obtained ranged from -11.27 to -15.90 Kcal/mol. According to pharmacokinetics and ADME study, all phenothiazine derivatives A-E, as well as Penicillin 10, have a bioavailability higher than zero, ranging between 0.17 and 0.55. Phenothiazine derivative A is similar to the reference drug penicillin 10, indicating that it is the most bioactive. [Display omitted]