Improved Syntheses, Crystal Structures Analysis, DFT Calculation, Anticancer and Antibacterial Properties of Some
Ahmed K Hijazi1,2, Qusai M Sarayrah2, Abdelrahman W Malkawi2
1Department of Chemistry, College of Arts and Sciences, University of Petra, P.O. Box 961343, Amman 11196, Jordan.
Abstract:
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).
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