N-Mannich Bases in the preparation of novel 4-(benzo[d]thiazol-2-yl)-5-phenylpyrrolidine-2,3-dione derivatives as potentially active antibacterial and antifungal agents

• Synthesis of benzothiazolyl pyrrolidine 2 and their corresponding N -Mannich bases. • Synthesis of phenolic Mannich base 14 and N -Mannich bases. • Studying the antimicrobial efficacy of the newly synthesized compounds with promising results which confirmed by docking. Compound 4-(benzo[d]thiazol-2-yl)-5-phenylpyrrolidine-2,3-dione (2) was taken as a precursor to synthesize some new N -Mannich bases 4, 7 , and 10 via the reaction of their corresponding Schiff bases 3, 6 , and 9 with formaldehyde and piperidine. Similarly, N -Mannich bases 5, 8 , and 11 were obtained by the reaction of their corresponding Schiff bases 3, 6 , and 9 with benzaldehyde and 3-aminopyridine, or 5-aminotetrazole, or 2-aminothiazole, respectively. Moreover, N -Mannich bases 15a-l were synthesized by direct reaction of compound 2 with formaldehyde and some secondary amines. In addition, N -Mannich base 14 was obtained from its corresponding phenolic Schiff base 13 which was obtained by the reaction of benzothiazole derivative 12 with p -hydroxyaniline. Also, phenolic N -Mannich base-bearing azonine dione moiety 18 was achieved by the reaction of 15f with p -hydroxyaniline followed by the reaction of formaldehyde and piperidine to give N -Mannich base 17 which was then subjected to periodate oxidation. The targeted compounds were synthesized and characterized by spectroscopic analysis and screened for antimicrobial evaluation as antibacterial and antifungal agents. The biological evaluation showed that N -Mannich bases with tetrazole, thiazole, and phenothiazine moieties are active against B. subtilis, S. aureus (Gram-positive bacteria), E. coli, P. aeruginosa (Gram-negative bacteria), and C. albicans (Fungi strain). Meanwhile, the molecular docking study was carried out on the highest antibacterial derivatives ( 7, 8, 11 , and 15g ) with a targeted PDB: 2eg7 protein. Our docking results disclose dissimilar binding types of interactions for each derivative, suggesting varying degrees of affinity and specificity towards the target protein.