Improved Syntheses, Crystal Structures Analysis, DFT Calculation, Anticancer and Antibacterial Properties of Some 4-(Benzylamino)benzoic Acid Derivatives

A series of 4-(benzylamino)benzoic acid derivatives ArCH₂NH-4-C₆H₄CO₂H (1–19) (Ar = C₆H₅ (1); 4–Cl–C₆H₄ (2); 4-NMe-C₆H₄ (3); 4–Br–C₆H₄ (4); 3-NO₂–C₆H₄ (5); 4-NO₂–C₆H₄ (6); 2-OMe-C₆H₄ (7); 3-OMe-C₆H₄ (8); 4-OMe-C₆H₄ (9); 2,3-OMe-C₆H₃ (10); 3,4-OMe-C₆H₃ (11); 2-OH, 3-OMe-C₆H₃ (12); 3-OMe, 4-OH-C₆H₃ (13); 3,5-OMe, 4-OH-C₆H₄ (14); 2-OH-5–Br–C₆H₃ (15), 3-OH-C₆H₄ (16); 4-SMe-C₆H₄ (17); 2,3-OH-C₆H₃ (18); 3-CF₃–C₆H₄ (19)) were synthesized via reductive amination of p-aminobenzoic acid with substituted benzaldehydes and sodium borohydride. The structures were confirmed by MS, FT-IR, NMR, and E.A., with single-crystal X-ray diffraction elucidating key intermolecular interactions in compounds 2, 4, 7–9 and 11. Hirshfeld surface analysis and 2D fingerprint plots highlighted noncovalent interactions contributing to crystal packing. DFT calculations (PBE0/def2-TZVP/CPCM) provided optimized geometries, HOMO–LUMO gaps, and electrostatic surface potentials. TD-DFT simulations supported experimental UV–vis spectra. Several derivatives (2, 3, 5, 7, 8, 10, 11, 13–16) showed moderate antibacterial activity (MIC = 64–128 μg/mL) against different strains of bacteria, while compound 18 exhibited promising anticancer activity with IC₅₀ values of 90.69 μM against Non-Small Cell Lung Cancer cell line (A549) and 32.22 μM against Small Cell Lung Cancer cell line (H69).