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

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide A series of 4-(benzylamino)benzoic acid derivatives ArCH 2 NH-4-C 6 H 4 CO 2 H ( 1–19 ) (Ar = C 6 H 5 ( 1 ); 4–Cl–C 6 H 4 ( 2 ); 4-NMe-C 6 H 4 ( 3 ); 4–Br–C 6 H 4 ( 4 ); 3-NO 2 –C 6 H 4 ( 5 ); 4-NO 2 –C 6 H 4 ( 6 ); 2-OMe-C 6 H 4 ( 7 ); 3-OMe-C 6 H 4 ( 8 ); 4-OMe-C 6 H 4 ( 9 ); 2,3-OMe-C 6 H 3 ( 10 ); 3,4-OMe-C 6 H 3 ( 11 ); 2-OH, 3-OMe-C 6 H 3 ( 12 ); 3-OMe, 4-OH-C 6 H 3 ( 13 ); 3,5-OMe, 4-OH-C 6 H 4 ( 14 ); 2-OH-5–Br–C 6 H 3 ( 15 ), 3-OH-C 6 H 4 ( 16 ); 4-SMe-C 6 H 4 ( 17 ); 2,3-OH-C 6 H 3 ( 18 ); 3-CF 3 –C 6 H 4 ( 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 IC 50 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).

Source: ACS Omega

DOI: 10.1021/acsomega.5c03898